Cortex

Naming pictures from the same semantic category can interfere with subsequent word retrieval. Although the left inferior frontal gyrus (LIFG) has been implicated in resolving this semantic interference, its causal role in this process remains unclear. Across three experiments, we investigated the contribution of the LIFG to interference resolution during blocked-cyclic naming. Experiment 1 tested whether continuous theta-burst stimulation over the LIFG increased semantic interference relative to vertex stimulation. Although the overall interference effect did not differ significantly between stimulation sites, exploratory analyses revealed an unexpected pattern based on the initial context (related vs. unrelated) with which items were named, suggesting that LIFG disruption affected retrieval of previously related items even when they were subsequently named in unrelated contexts. This observation motivated two further experiments examining the consequences of prior naming context more directly. Experiment 2 established that, without stimulation, interference observed in related blocks was no longer evident after the items were redistributed into unrelated blocks. Experiment 3 combined this design with cathodal or sham transcranial direct current stimulation (tDCS) over the LIFG. Planned comparisons showed that cathodal stimulation slowed naming of initially related items both within related blocks and after redistribution into unrelated blocks; corresponding comparisons for items named consistently in unrelated blocks were not significant. The similar patterns across two stimulation methods suggest that LIFG-mediated control may influence both selection under current competition and subsequent retrieval of previously competing words. These findings could be accommodated within a hybrid account in which working memory supports context-guided selection and selection-related control helps recalibrate lexical accessibility, limiting the carryover of interference into subsequent naming.

Task demand has a long-standing history in experimental psychology, with numerous investigations of the capacity of different systems and processes under varying cognitive load. Whilst demand is a broadly used term in the literature, it is limited by a lack of cross-domain operationalisation, and thus can be a confound in many inter-domain investigations. To address this, we generated and validated two large-scale, open-source, widely applicable stimuli sets that: (i) can probe a wide, continuous range of objective behaviourally-measured processing demand, and (ii) can be directly matched across two highly contrastive cognitive domains (semantic and visuospatial processing). We normed these tasks in a large, online cohort of healthy adults, enabling future studies to utilise and benefit from reliable baseline measures of demand. Using a matching algorithm that takes into account both speed and accuracy, we then closely paired each semantic judgement trial with a trial of comparable difficulty from the corresponding visuospatial task to produce a cross domain matched set of over 400 items. Finally, we analysed the psycholinguistic and perceptual properties of these stimuli to explore some of the underlying factors driving demand.

Understanding how the brain represents meaning at different levels of specificity, from general categories (bird) through combined phrases (nocturnal bird) to specific exemplars (owl), is a central question in semantic cognition and its disorders. The anterior temporal lobes (ATL) have been implicated in both activating stored conceptual representations and combining them, yet whether these two routes to conceptual content engage the ATL in the same way remains an open question. We recorded concurrent MEG-EEG from 36 participants reading 100 conceptual triads varying parametrically in specificity: general words (bird), adjective-noun phrases (nocturnal bird), and specific words (owl). Source analyses revealed a non-linear pattern in bilateral ATL (400-520ms): high-specificity concepts elicited greater activity than both low-specificity words and mid-specificity phrases. Bilateral inferior frontal cortex showed this effect with similar timing (430-630ms). N400 amplitude and ATL source activity showed a functional dissociation in their sensitivity to word frequency, ruling out a purely frequency account of the ATL and IFC effects. Results imply that accessing high-specificity concepts requires individuating stored representations among competitors, whereas phrases construct meaning through a different route. These findings extend the unified semantic hub account by revealing that computational operations within the ATL vary depending on task and stimulus demands.

Chronic spatial neglect after right-hemisphere stroke reflects network dysfunction, with recovery influenced by structural connectivity. Music recruits coordinated bi-hemispheric activity and may promote interhemispheric communication after stroke. Following our pilot study in post-stroke aphasia, we asked whether classical music modulates connectivity and behavior in chronic neglect. Three patients completed a crossover protocol comparing two weeks of daily audiovisual classical music with an audiobook control, with neglect, mood, quality-of-life, diffusion MRI, and resting-state high-density EEG measures. All showed right superior longitudinal fasciculus II disconnection with preserved callosal pathways. In N2, line bisection shifted leftward across all five lines after music, together with increased posterior interhemispheric theta-band weighted symbolic mutual information (wSMI), then deteriorated into the pathological range after the audiobook, without mood improvement. N1 showed mixed behavioral effects, with mood and quality of life improving after music. N3 showed no significant spatial improvement and worsened mood after music. These heterogeneous responses motivate larger studies of connectional predictors. The findings support the feasibility of classical music as an adjunct to neglect rehabilitation and suggest that cognitive changes may occur independently of mood, while the audiobook cannot be considered an inert control.

Efficient motion perception requires integrating immediate sensory evidence with internal representations shaped by experience. This influence of recent history can produce serial dependence effects (SDEs), in which current judgments are biased toward or away from the source of previous information. We examined SDEs in auditory, visual, and cued audiovisual motion-direction discrimination using aggregate psychometric measures and trial-level generalized linear mixed-effects models (GLMMs), which estimated the independent contributions of the previous stimulus direction and the participant's previous response. Participants completed unisensory (n=57) and cued audiovisual (n=48) motion-discrimination tasks. Aggregate analyses indicated attractive SDEs in auditory conditions, repulsive SDEs in visual conditions, and no net SDE in the audiovisual-cued condition. Trial-level modeling revealed a more nuanced structure: previous stimulus direction produced repulsive effects in both unisensory conditions, with previous visual direction influencing judgments across all conditions containing visual motion, whereas previous response produced attractive effects only when visual information was task-relevant. In the audiovisual-cued condition, the absence of a net psychometric shift was consistent with the opposing influences of an attractive response-history effect and a repulsive visual stimulus-history effect rather than an absence of serial dependence. These findings suggest that serial dependence in motion perception reflects dissociable and concurrently operating processes, including a predominantly visual, adaptation-like stimulus-history effect and a task-dependent, decision-related response-history effect.

Unveiling the plastic mechanisms of the primary visual cortex (V1) is crucial for understanding how visual processing can change and adapt, ultimately informing interventions to promote functional recovery following visual system damage. Paired associative stimulation (PAS) protocols can induce associative plasticity within the human V1. However, previous paradigms used full-field visual stimulation, engaging both hemispheres simultaneously, leaving unclear whether plasticity can be selectively targeted to a single visual pathway and whether it can modulate the non-stimulated hemisphere. Across three experiments in healthy participants, we investigated the neurophysiological, behavioural, and interhemispheric outcomes of a novel lateralized visual PAS protocol (vPAS). Pattern-reversal checkerboards were presented in a single visual hemifield and time-locked to transcranial magnetic stimulation (TMS) pulses delivered over the contralateral V1. Experiment 1 assessed neurophysiological effects by recording hemifield-lateralized visual-evoked potentials (VEPs) and testing three inter-stimulus intervals (ISIs: 75, 100, and 125 ms) between vPAS-paired stimuli. Experiment 2 evaluated perceptual changes in contrast detection, while Experiment 3 examined vPAS hemispheric specificity and aftereffects on interhemispheric visuomotor transfer. Only the 75-ms ISI consistently modulated visual processing in the non-conditioned hemisphere, reducing N75 amplitude and improving contrast detection for visual stimuli presented contralateral to the TMS side. Longer ISIs were not effective. Furthermore, this protocol altered interhemispheric transfer exclusively when the left, but not the right, V1 was targeted during vPAS. In conclusion, lateralized vPAS induces timing-dependent changes beyond the stimulated cortex, suggesting that associative plasticity can engage contralateral visual circuits and modulate visual processing.

Eye movements have been shown to reveal the cognitive processes underlying spatial ability, but most studies investigating gaze behaviour in spatial cognition use a single, screen-based task. Therefore, it is unknown whether these gaze behaviours are preserved across naturalistic task environments, or whether their relationship with spatial performance is domain-general or task-specific. The present study tested whether established gaze behaviours are preserved and generalizable across diverse, naturalistic spatial tasks. N = 30 young adults completed three naturalistic spatial tasks varying in perceptual, cognitive, and visuomotor demands: Q-bitz, the Brick Building Task (BBT), and the Mental Rotation Test (MRT). Gaze was measured using the Pupil Labs Neon eye tracker. Within-task analyses were conducted to assess whether gaze behaviours were preserved, and cross-task analyses were conducted to assess the generalizability of preserved gaze behaviours. Within-task analyses identified source inspection and transition rate as gaze behaviours that were consistently sensitive to changing task demands. Cross-task analyses showed that source fixation duration was a domain-general predictor of performance, whereas the relationship between transition rate and performance differed by task. Exploratory sex-separated analyses also suggested a more consistent gaze-performance relationship in males. These findings show that source fixation duration may represent a common cognitive process underlying performance across naturalistic spatial tasks.

Motor imagery and overt action are proposed to share common planning mechanisms while relying on distinct processes during movement performance. To investigate how repetition affects physical and imagined movements, participants physically or mentally drew paths while avoiding barriers. The barrier orientations were either repeated or different across consecutive trials, and the modality (execution or imagery) of the trials either changed or remained the same for two consecutive trials. Reaction time and movement time were analysed as measures of movement planning and task performance, respectively. Imagined movements produced longer reaction times and movement times than physical movements. Repetition of orientation reduced reaction times in both physical and imagined trials, indicating that trajectory repetition facilitated movement preparation. In contrast, previous trial type influenced reaction times only for physical movements, which were only initiated faster when preceded by another physical trial. Different effects emerged for movement time. Physical movements were faster when the same trajectory was repeated no matter the previous trial type, whereas imagined movements were unaffected by orientation and instead showed shorter durations when preceded by another imagined trial. The findings indicate that physical and imagined movements rely on more similar trajectory representations during the planning stage, but diverge during task performance. While physical movements appear to benefit from the persistence of previously generated movement trajectories, imagined trials seems more influenced by modality-specific cognitive processes. These results provide behavioural support for the Motor-Cognitive model and contribute to understanding how movement repetition influences overt and imagined actions.

Chinese is one of the living languages with the highest homophone densities, making homophone processing a critical component of language comprehension and orthographic decoding, as well as an ideal model for examining its cognitive mechanisms. This study assessed mono- and bi-character homophone selection function in 129 Mandarin- and Cantonese-speaking participants, including 66 cognitively healthy individuals, 17 with semantic variant (sv) primary progressive aphasia (PPA), 23 with the nonfluent/agrammatic variant (nfv) PPA, and 23 with the logopenic variant (lv) PPA. All PPA variants showed impairment in homophone selection, with most significant deficits in svPPA and lvPPA. ROC analyses demonstrated its strong diagnostic utility for distinguishing PPA from controls. Voxel-based morphometry revealed that homophone performance correlated with gray-matter volume in left anterior and inferior temporal regions, with variant-specific patterns observed. These findings described the potential role of homophone selection in diagnosing PPA syndrome in Chinese speakers, illuminate crosslinguistic influences on language impairment in PPA, and provide novel insights into the cognitive processing of homophones.

ObjectiveRecovery from post-stroke aphasia is traditionally thought to plateau within a year after stroke. As such, no studies have characterized long-term recovery using comprehensive behavioral assessment and longitudinal functional MRI. We sought to characterize behavioral and neuroplastic changes over nearly six years in a patient with chronic post-stroke aphasia. MethodsA patient with chronic left hemisphere stroke underwent behavioral assessment and task-based fMRI at 9, 22, 33 and 71 months after stroke. Testing assessed auditory comprehension, semantic and phonological processing, naming, reading, spelling, motor speech, and executive function. Task-related activation during an adaptive semantic matching paradigm was quantified within language and semantic regions of interest. ResultsBehavior improved across multiple language domains. WAB-R Aphasia Quotient increased from 49.2 to 69.2, along with the large gains in word finding, connected speech, reading and spelling, whereas auditory comprehension remained relatively stable. fMRI demonstrated progressively increasing activation within left-hemisphere language regions, reaching normative range by the final assessment, along with increasing activation in semantic/executive regions. DiscussionRecovery of language production abilities can continue for years after stroke, supported by neuroplastic changes in the brain. Neurologists should inform stroke survivors that aphasia recovery can continue indefinitely after stroke.

The duration of visual stimuli can be altered by stimulus features, such as size, brightness, and motion. Recently, we observed that motion-induced changes in perceived duration also shift confidence judgments, but do not track awareness of the illusion. How these two effects differ and are instantiated neurally are unknown. We investigated this question by replicating our previous finding, in which human subjects (n=27) performed a temporal bisection task where they were asked to classify the duration (1-3.5s) of a walking stickman figure with different velocities and provide confidence judgments while 64-channel electroencephalogram (EEG) activity was recorded. Behavioral findings replicated the previous time dilation effect where progressively faster walking speeds led to longer perceived durations. A similar shift was observed for confidence ratings, yet with lowest confidence for the medium walking speed, indicating a metacognitive inability to monitor dilation. Furthermore, common EEG signatures of time perception, such as the late positive component of timing (LPCt) and contingent negative variation (CNV) did not vary with walking speed. Instead, onset-locked responses over occipital electrodes covaried with walking speed and correlated with subject-level shifts in psychometric functions, but not with confidence; conversely, frontocentral responses covaried with confidence judgments, but not walking speed. These findings suggest that temporal illusions are engaged by sensory processes that fail to reach the metacognitive level and that confidence judgments, in turn, are driven by motor estimates read out from frontocentral regions

In aphasia, variability in lesion location and post-stroke network reorganization complicates efforts to identify the regions that support semantic versus phonological processing. In prior work, researchers have often examined these domains in separate patient cohorts, further limiting direct comparison of their neural substrates within aphasia. To address this gap, we investigated the degree of overlap and specialization within semantic and phonological networks in adults with and without aphasia and examined how neural activity relates to task performance and lesion profiles. Sixteen neurologically healthy adults and 15 participants with aphasia following left hemisphere stroke completed adaptive Semantic Matching and Rhyme Judgment tasks during functional near-infrared spectroscopy (fNIRS) recording. Changes in oxyhemoglobin and deoxyhemoglobin were measured within regions of interest, and activation was related to standardized task performance and damage to left ventral and dorsal language pathways in participants with aphasia. Controls showed largely distinct activation patterns consistent with prior fMRI findings: Semantic Matching preferentially recruited ventral stream regions, particularly left temporal cortex, whereas Rhyme Judgment more strongly recruited dorsal regions, including left inferior frontal and inferior parietal cortex. Participants with aphasia showed greater inter-individual variability and no clear group-level segregation of dorsal and ventral activity. Better Semantic Matching performance was associated with less left ventral stream damage and greater left dorsal activation, whereas better Rhyme Judgment performance was associated with lower right hemisphere ventral and dorsal activation. These findings suggest that post-stroke language performance reflects residual specialization, lesion-dependent constraints, and flexible recruitment of surviving tissue. Overall, fNIRS shows promise as an alternative to fMRI for language mapping in post-stroke aphasia, although replication in larger samples with more extensive cortical coverage is warranted.

Navigating the world requires our brains to constantly process a massive influx of information from the environment. One of the most remarkable yet complex feats the human brain performs daily is speech perception. It is a multifaceted, hierarchical process that relies heavily on the integration of auditory and visual cues, particularly in noisy environments. Neural integration of these streams is hypothesized to depend on temporal mechanisms governed by individual alpha frequency (IAF, 8-12 Hz), which serves as a key neural correlate of the temporal binding window (TBW). While IAF has been linked to multisensory integration, its role in shaping multisensory illusions remains largely unexplored. Here, we tested this directly using transcranial alternating current stimulation (tACS) to modulate occipital activity during multisensory conflict. In a two-day protocol involving 27 healthy participants, resting-state EEG was recorded to determine IAF. On Day 2, participants then performed a multisensory speech task involving congruent (pa/, /ta/, /ka/) and incongruent McGurk stimuli (auditory /pa/, visual /ka/), both at baseline and during tACS applied at IAF and offset frequencies (IAF +/- 2 Hz) over occipital electrodes. While accuracy for congruent syllables remained high across conditions, results revealed that tACS significantly reduced the perception of illusory /ta/ percepts during McGurk trials. Finally, using a phenomenological model based on Kuramoto oscillators, we provided a mechanistic explanation for the percentage of illusory responses observed across participants under the influence of tACS at IAF and offsets. This study highlights the potential for targeted neuromodulatory interventions to influence multisensory processing in clinical or professional settings.

Neuroimaging studies have identified a specialised social brain network that supports emotion recognition and social cognition. This network performs a range of functions that include facial expression recognition and inferring the mental states of others. Studies of neuropsychological patients report that damage to the right inferior frontal gyrus (IFG), the top-down control area in this network, impairs facial expression recognition. To investigate how transient disruption of the right IFG affects the wider social brain we combined transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI). Participants (n=20) were scanned across two sessions while performing a delayed match-to-sample emotion recognition task in which happy or fearful expressions were preceded by a congruent or incongruent word cue. Prior to each scan, thetaburst TMS was delivered over the right IFG or over the vertex control site (session order was balanced across participants). A group whole-brain analysis revealed that TMS to the IFG increased neural activity in multiple regions of the social brain network. These included the bilateral temporal pole, precuneus and medial prefrontal cortex (mPFC). This pattern of results shows that the disruption of top-down control mechanisms localised in the IFG alters the neural processing in remote nodes of the social brain network. Our findings are discussed within the wider context of how we recognise and understand the emotions of other people.

Background and Objective: For their acceptance as endpoints in clinical trials, biomarkers and clinical outcome assessment (COA) measures should show reliability by being reproducible (precise) and responsive to change. We evaluated precision and responsiveness of MRI-derived brain volume metrics and various COAs in ceroid-lipofuscinosis, neuronal-3 (CLN3) disease. Methods: This longitudinal observational study (NCT03307304) included 44 individuals with CLN3-related disease (ages 0.5-29.1 years, 48% female). Brain volumetric measures were computed using SynthSeg-v2.0 from T1-weighted 3D MPRAGE images acquired at 3T (Median [Q1, Q3] total MRI follow-up duration from baseline: 2.04 [0.00, 3.69] years). Compartmental tissue volumes were normalized to a model-adjusted total intracranial volume and scaled to the tissue-specific volume fraction expected in healthy adolescent brains to extract measures of brain atrophy. COAs included the Vineland Adaptive Behavior Scales, verbal IQ, and the Unified Batten Disease Rating Scale (UBDRS). Analysis of linear mixed-effects models included only CLN3 participants with syndromic presentation, having three or more visits per measurement to estimate slope, its relative standard error (RSE), and the minimum inter-visit interval (Tmin) for statistically significant progression for each participant. Tmin to detect progression in 75% of the population (Tmin,75%) was computed for each metric. Results: Among brain volumetric measures, brain parenchyma volume (BPV) and gray matter volume (GMV) were the most precise and responsive metrics. BPV showed an overall intra-individual decline with age of -1.32%/year (95% CI: -1.64% to -0.99%), low RSE of 12.5%, and short Tmin,75% of 0.85 years (95% CI: 0.47-1.24). Amongst COAs, the UBDRS Clinical Global Impression (CGI) score was the most precise and responsive with an overall intra-individual increase of 1.26 units/year (95% CI: 1.03-1.49), RSE of 24.10%, and Tmin,75% of 2.56 years (95% CI: 1.73-3.46), though with lower precision (RSE higher) and lower responsiveness (Tmin,75% longer) than BPV. Discussion: MRI-derived metrics, in particular BPV and GMV, detected change in brain atrophy with high precision and responsiveness suggesting that they would be informative for evaluating potential neuroprotective therapies in CLN3 disease. These findings support incorporating MRI-derived volumetric measurements alongside clinical assessments in future clinical trials in CLN3.

Communication is inherently interactive, yet most neuroimaging studies examine individuals in isolation. Here, we used functional near-infrared spectroscopy (fNIRS) hyperscanning to investigate interbrain synchrony (IBS) during naturalistic communication. In Study 1, 13 healthy familiar dyads completed Joint Singing, Joint Reading, and Picture Guessing tasks. IBS was quantified using wavelet transform coherence across bilateral frontal and temporoparietal regions. Joint Singing produced higher IBS than the other tasks in several regions, including the dorsolateral prefrontal cortex and temporoparietal junction, and selected effects were greater in true than pseudo-dyads. In Study 2, we applied the same paradigm to five individuals with chronic post-stroke aphasia interacting with trained speech-language pathologists. IBS could be estimated in all dyads after lesion-informed channel exclusion, although regional coverage varied with lesion location. These findings demonstrate that fNIRS hyperscanning can capture task-dependent interpersonal neural coupling during spoken interaction and can be extended to communication involving individuals with aphasia. This approach provides a foundation for studying how neural coordination between communication partners relates to functional communication and partner-supported interaction.

Older adults typically exhibit reduced episodic memory precision, while maintaining relatively preserved retrieval success. However, little is known about whether these age-related differences are influenced by internal biological factors (e.g., chronotype) or external testing conditions (e.g., experiment format, time of day). To address this question, younger and older adults completed an object-location memory task online, either in the morning or evening, and either with or without video-based supervision. Memory performance was assessed using mean absolute error and Bayesian hierarchical mixture modelling, which dissociated memory precision ({kappa}) from the probability of memory-based responding ({theta}). Immediate memory performance was high across age groups, irrespective of time of day. Greater encoding error predicted greater retrieval error, and participants tested in the video condition exhibited lower recall error and higher recognition performance than those tested without supervision. Consistent with prior studies, older adults exhibited reduced memory precision relative to younger adults, whereas retrieval success remained largely intact. However, Bayesian Hierarchical Modelling provided no evidence that time of day, experiment format, or their interactions with age influenced either memory precision or retrieval probability. Older adults reported stronger morning preferences than younger adults, and participants generally selected testing times that aligned with their chronotype. Nevertheless, alignment between chronotype and testing time did not modulate memory performance. The results indicate that age-related differences in episodic memory precision are robust across variations in testing context, including time of day, experiment format, and individual differences in chronotype. More broadly, the results support the feasibility of remote and unsupervised testing for memory precision research and suggest that chronotype and testing time are unlikely to be major sources of variability in immediate object-location memory performance.

Motor effort has been shown to bias perceptual decisions toward less effortful choices, but it remains unknown whether this bias already takes effect during the early stages of decision formation through preparatory attentional allocation or sensory processing, or during later-stage evidence accumulation preceding response execution. This study investigated when motor effort becomes integrated into decision formation by focusing on the temporal evolution of neural processing during perceptual decision-making. While 64-channel EEG was recorded, twenty-four healthy adults performed an orientation discrimination task in which two Gabor patches appeared simultaneously in the left and right visual hemifield and decisions were reported using two pressure-sensitive response buttons requiring different levels of force. We found that motor effort modulated EEG activity at both the preparatory and later decision stages: pre-stimulus alpha power was reduced over the occipito-parietal cortex contralateral to the low-effort option, and mean centro-parietal positivity (CPP) amplitude preceding response execution was greater over centro-parietal cortex for low-effort choices, while leaving early sensory representations intact as indicated by no differences in P1 or N1 amplitude following stimulus onset. Trial-by-trial CPP amplitude preceding response execution increased with the likelihood of selecting the low-effort option, whereas the pre-stimulus alpha modulation was not associated with behavioral decision bias. These findings suggest that motor effort biases perceptual decisions primarily during later-stage evidence accumulation, thereby providing insight into the neural basis of embodied perceptual decision making.

Purpose: This study examined whether word-based and non-word natural language sampling (NLS) measures complement standardized language scores in characterizing expressive communication among preschool children with autism with language impairment (AUT-LI), Down syndrome (DS), and fragile X syndrome (FXS). Method: Participants included 82 preschool children with AUT-LI (n = 32), DS (n = 34), or FXS (n = 16). Expressive communication was characterized using the Preschool Language Scales and 10-minute natural language samples collected during a standardized play-based protocol. NLS measures included traditional word-based metrics, such as lexical diversity, intelligibility, and word approximations, as well as tiered non-word vocalization measures, including non-speech, single-phoneme, and multi-phoneme vocalizations. Analyses examined age associations, diagnostic group differences, between group differences in variability, and exploratory communication profiles derived using principal component analysis and partitioning around medoids clustering. Results: Diagnostic groups did not significantly differ on standardized expressive language scores. Children with FXS showed higher performance than the AUT-LI and DS groups on several word-based NLS measures, whereas non-word vocalization measures primarily revealed differences in within-group variability. Word-based NLS measures were consistently associated with standardized expressive language skills, while associations for non-word vocalizations varied by vocalizations type. Cluster-validity indices factored a two-cluster solution. A hypothesis-informed three cluster solution that included non-word vocalizations suggested Higher Language, Lower Output, and High Output-Low Structure profiles. Conclusions: Standardized and NLS measures provide complementary descriptions of expressive communication in children with neurodevelopmental disorders. Non-word vocalization coding may be especially useful for describing clinical meaningful variation among children with limited expressive language. Keywords: Natural language sampling; expressive language; neurodevelopmental disorders; autism spectrum disorder; Down syndrome; Fragile X syndrome

Syntax processing impairment is a defining feature of primary progressive aphasia (PPA), particularly in the nonfluent/agrammatic variant. However, current models are derived largely from Indo-European languages, and it remains unclear whether the cognitive and neuroanatomical mechanisms of syntax processing generalize to Chinese, an analytic, pro-drop language that encodes grammatical relationships primarily through word order and function words rather than inflectional morphology. Participants were recruited from the international Chinese Language Assessment in PPA cohort and included 64 individuals with PPA (19 logopenic, 15 nonfluent/agrammatic, 15 semantic, and 15 unclassifiable/mixed) and 60 cognitively healthy controls. Participants completed sentence comprehension and production tasks with systematically manipulated syntactic features. Item-level linguistic determinants were examined using ridge regression, diagnostic performance using receiver operating characteristic analyses, and neuroanatomical correlates using voxel-based morphometry of structural MRI. Performance on sentence comprehension and production was influenced by grammatical and lexical features. Subject-relative clauses, passive constructions, a higher proportion of function words, longer character length, and greater lexical content were associated with poorer performance among participants with PPA. Sentence comprehension was impaired in the logopenic, nonfluent/agrammatic, and semantic variants, even when isolated to the syntactic component of the sentence comprehension task. Similarly, sentence production was impaired across all PPA variants (all P < 0.01 versus controls). No significant differences were observed among PPA variants. Adjusted receiver operating characteristic analyses demonstrated high discrimination between each PPA variant and controls, with areas under the curve ranging from 0.87 to 0.97 for sentence comprehension-syntax and from 0.91 to 0.97 for sentence production. However, pairwise comparisons showed no significant differences in discriminative performance among PPA variants after correction for multiple comparisons. Both sentence comprehension-syntax and sentence production showed associations with semantic and repetition measures in addition to motor speech measures. Voxel-based morphometry showed that higher sentence comprehension-syntax scores were associated with greater grey matter volume in left frontotemporal and cingulate regions, whereas higher sentence production scores were additionally associated with greater gray matter volume in frontostriatal structures, including the caudate, putamen, and thalamus. Syntactic processing impairment in Chinese-speaking individuals with PPA extends beyond the nonfluent/agrammatic variant and is associated with distributed frontotemporal and frontostriatal regions, as well as lexical-semantic and auditory verbal short term memory mechanisms. These findings suggest that the cognitive and neural manifestations of syntactic impairment may be shaped by language-specific typological properties, underscoring the need for linguistically informed approaches to the assessment and interpretation of PPA.