Speaking in Tones: The role of lexical tones in Chinese-speaking Primary Progressive Aphasia

Two-thirds of the world’s 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.

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 “tone-twister” 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.

Participants with nonfluent/agrammatic variant PPA (nfvPPA) showed marked impairments in lexical tone production (all p<0.001), with a disproportionately high rate of tonal relative to syllabic errors (p<0.001). In contrast, semantic variant PPA (svPPA) exhibited prominent deficits in three tone perception tasks (all p<0.001). Patients with logopenic variant PPA (lvPPA) showed relatively preserved tone production but a predominance of syllabic errors (p<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.

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. Competing Interest Statement The authors have declared no competing interest. Funding Statement The work is supported by the Global Brain Health Institute (GBHI ALZ UK-19-589585), Alzheimers Association (AACSFD-22-972143), University of California, San Francisco, National Institutes of Health (NIA R21AG068757, R01AG080469, R01AG083840, U19AG079774, P01AG019724, U01NS128913, NIDCD K24DC015544, RF1NS050915, R01 NS100440-01, R01AG058233), Alzheimers Disease Research Center of California (P30 AG062422). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Participants were recruited from seven sites in Hong Kong, Taiwan, and the United States. The study protocol was approved by the respective institutional review boards, specifically ethics committees at National Taiwan University Hospital (Taipei and HsinChu), University of California, San Francisco, Chinese University of Hong Kong, Education University of Hong Kong, En Chu Kong Hospital, Buddhist Tzu Chi Hospital. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Anonymized data are available from the corresponding author upon request and subject to approval and completion of a Material Transfer Agreement. Data are not publicly accessible in accordance with institutional ethical protocols governing participant confidentiality.