Cortex

The ability to speak coherently, maintaining focus on the topic at hand, is critical for effective communication and is commonly impaired following brain damage. Recent data suggests that executive processes that regulate access to semantic knowledge (i.e., semantic control) are critical for maintaining coherence during speech. To test this hypothesis, we assessed speech coherence in a case-series of stroke patients who exhibited deficits in semantic control. Patients were asked to speak about a series of topics and their responses were analysed using computational linguistic methods to derive measures of their global coherence (the degree to which they spoke about the topic given) and local coherence (the degree to which they maintained a topic from one utterance to the next). Compared with age-matched controls, patients showed severe impairments to global coherence but not to local coherence. Global coherence was strongly correlated with the patients performance on tests of semantic control, with greater semantic control deficits associated with poorer ability to maintain global coherence. Other aspects of speech production were also impaired but were not significantly correlated with semantic control deficits. These results suggest that semantic control deficits give rise to speech that is poorly regulated at the macrolinguistic "message" level. The preservation of local coherence in the patients suggests that automatic activation of semantic associations is relatively intact, such that each utterance they produce is connected meaningfully to the next. However, in the absence of control processes to constrain semantic activation, the content of their speech becomes increasingly distant from the original topic of discourse. This study is the first to investigate the impact of semantic control impairments on speech production at the discourse level and suggests that patients with these impairments are likely to have difficulties maintaining coherence in conversation.

Recent studies highlight a critical role of the human lateral occipitotemporal cortex (LOTC) in action understanding, particularly in how we perceive and interpret movements and interactions with tools and bodies. This region, along with connected fronto-parietal areas, has been implicated in limb apraxia, a disorder that affects skilled movement after stroke. In this study, we focused on whether there were any changes in brain activity or connectivity in areas involving the LOTC and its interconnected perceptuo-motor network after left hemisphere stroke, a common cause of limb apraxia. We recruited 29 stroke patients and 19 age-matched healthy participants. Using functional neuroimaging, we asked participants to observe static photographs of familiar tools, bodies, non-tool objects, and scrambled images while performing a simple attention task (1-back task). The goal was to map the brain areas specifically involved in tool-related and body-related visual processing. Whole-brain analysis revealed activity changes related to tool and body stimuli in the LOTC and fronto-parietal regions. Interestingly, there were no significant differences in activation between stroke patients and controls based on the overall whole-brain analysis. However, deeper analyses revealed critical group-related differences. Using representational similarity analysis (RSA), we found that stroke patients showed reduced ability to discriminate between tools and non-tools within the right LOTC. Psychophysiological interactions (PPI) analysis further indicated increased connectivity between the left inferior parietal sulcus (IPS) and the left LOTC in stroke patients during tool-related tasks, a finding that correlated with their performance on meaningless imitation apraxia task. Our findings suggest that limb apraxia after stroke is associated with altered representation of tools and functional connectivity in the perceptuo-motor network, particularly involving parietal and occipitotemporal regions. These results suggest perceptual deficits may be more relevant than previously reported in limb apraxia after stroke. HighlightsO_LIConsistent activations in the lateral occipitotemporal cortex (LOTC) were identified during tool and body localizer tasks in both stroke patients and healthy controls. C_LIO_LIRepresentational similarity analysis (RSA) revealed reduced discrimination between tools and non-tools in the right LOTC of stroke patients. C_LIO_LIDifferential task-related functional connectivity was observed between the LOTC and intraparietal sulcus (IPS) regions in stroke patients compared to controls during the tools localizer task. C_LI These findings provide insights into altered neural representations and connectivity underlying limb apraxia following left hemisphere stroke.

Cross-linguistic studies with healthy individuals are vital, as they can reveal typologically common and different patterns while providing tailored benchmarks for patient studies. Nevertheless, cross-linguistic differences in narrative speech production, particularly among speakers of languages belonging to distinct language families, have been inadequately investigated. Using a picture description task, we analyze cross-linguistic variations in connected speech production across three linguistically diverse groups of cognitively normal participants--English, Chinese (Mandarin and Cantonese), and Italian speakers. We extracted 28 linguistic features, encompassing phonological, lexico-semantic, morpho-syntactic, and discourse/pragmatic domains. We utilized a semi-automated approach with Computerized Language ANalysis (CLAN) to compare the frequency of production of various linguistic features across the three language groups. Our findings revealed distinct proportional differences in linguistic feature usage among English, Chinese, and Italian speakers. Specifically, we found a reduced production of prepositions, conjunctions, and pronouns, and increased adverb use in the Chinese-speakers compared to the other two languages. Furthermore, English participants produced a higher proportion of prepositions, while Italian speakers produced significantly more conjunctions and empty pauses than the other groups. These findings demonstrate that the frequency of specific linguistic phenomena varies across languages, even when using the same harmonized task. This underscores the critical need to develop linguistically tailored language assessment tools and to identify speech markers that are appropriate for aphasia patients across different languages.

The mechanism by which information is bound together in working memory is a central question for cognitive neuroscience. This binding is transiently disrupted during periods of post-traumatic amnesia following significant head injuries. The reason for this impairment is unclear but may be due to electrophysiological changes produced by head impacts. These are common and include pathological low frequency activity, which is associated with poorer neurological outcomes and may disrupt cortical communication. Here, we investigate associative memory binding during post-traumatic amnesia and test the hypothesis that misbinding is caused by a disruption in cortical communication produced by the pathological slowing of brain activity. Thirty acute moderate-severe traumatic brain injury patients (mean time since injury = 10 days) and 26 healthy controls were tested with a precision working memory paradigm that required the association of object and location information. A novel entropy ratio measure was calculated from behavioural performance. This provided a continuous measure of the degree of misbinding and the influence of distracting information. Resting state EEG was used to assess the electrophysiological effects of traumatic brain injury. Patients in post-traumatic amnesia showed abnormalities in working memory function and made significantly more misbinding errors than patients who were not in post-traumatic amnesia and controls. Patients showed a higher entropy ratio in the distribution of spatial responses, indicating that working memory recall was abnormally biased by the locations of non-target items suggesting a specific impairment of object and location binding. Slow wave activity was increased following traumatic brain injury. Increases in the delta-alpha ratio indicative of an increase in low frequency power specifically correlated with binding impairment in working memory. In contrast, although connectivity was increased in the theta band and decreased in the alpha band after traumatic brain injury, this did not correlate with working memory impairment. Working memory and electrophysiological abnormalities both normalised at six-month follow-up, in keeping with a transient increase in slow-wave activity causing post-traumatic amnesia that impaired working memory function. These results show that patients in post-traumatic amnesia show high rates of working memory misbinding that are associated with a pathological shift towards lower frequency oscillations.

Past research has shown that the bilateral dorsolateral prefrontal cortices (dlPFC) are implicated in both emotional processing as well as cognitive processing,1,2,3 in addition to working memory4, 5. Exactly how these disparate processes interact with one another within the dlPFC is less understood. To explore this, researchers designed an experiment that looked at working memory performance during fMRI under both emotional and non-emotional task conditions. Participants were asked to complete three tasks (letters, neutral images, emotional images) of the Sternberg Sorting Task under one of two trial conditions (sort or maintain). Regions of interest consisted of the left and right dlPFC as defined by brain masks based on NeuroSynth6. Results showed a significant main effect of the sort condition on reaction speed for all three trial types, as well as a main effect of task type (letters) on accuracy. In addition, a significant interaction was found between trial type (sort) and task type (letters), but not for either of the picture tasks. These results reveal a discrepancy between BOLD signal and behavioral data, with no significant difference in BOLD activity during image trials being displayed, despite longer response times for every condition. While these results show that the dlPFC is clearly implicated in non-emotional cognitive processing, more research is needed to explain the lack of BOLD activation seen here for similar emotionally valanced tasks, possibly indicating involvement of other brain networks.

Verbal fluency tasks are often used in neuropsychological research and may have predictive and diagnostic utility in psychiatry and neurology. However, researchers using verbal fluency have uncritically assumed that there are no category-or phoneme-specific effects on verbal fluency performance. We recruited 16 healthy young adult subjects and administered two semantic (animals, trees) and phonemic (K, M) fluency tasks. Because of the small sample size, results should be regarded as preliminary and exploratory. On the animal compared to the tree task, subjects produced significantly more legal words, had a significantly lower intrusion rate, significantly shorter first-response latencies and final silence periods, as well as significantly shorter between-cluster response latencies. These differences may be explained by differences in the category sizes, integrity of the categories borders, and efficiency of the functional connectivity between subcategories. On the K compared to the M task, subjects produced significantly more legal words and had significantly shorter between-cluster response times. Counterintuitively, a corpus analysis revealed there are more words starting with [<]m[>] compared to [<]k[>] in the experimental language. Our results potentially have important implications for research utilizing verbal fluency, including decreased reproducibility, questionable reliability of diagnostic and predictive tools based on verbal fluency, decreased knowledge accumulation, and increased number of publications with potentially misleading clinical interpretations.

IntroductionSustained attention and inhibition processes are fundamental components of attention that mature during adolescence, a transitive period between childhood and adulthood characterized by a rapid behavioral and cognitive development. The current study aimed to provide a better understanding of sustained attention and inhibition processes in typically developing adolescents (n = 26) aged 11-18. MethodsFunctional magnetic resonance images (fMRI) were acquired during two different modalities (the face and the scene) from a previously validated gradual{square}onset continuous (gradCPT) paradigm to evaluate sustained attention performances. In addition, we performed linear regression analyses to investigate how cerebral activation varied as a function of covariates of interest. ResultsWe showed a bilateral fronto-parieto-occipito brain activation during response inhibition regardless the type of task. Participants demonstrated better behavioral performances during the scene gradCPT. We observed a mainly left-lateralized pattern of activation in a fronto-cingulo-cerebellum area during the face gradCPT and an extended bilateral fronto-temporo-parieto-occipital activation during the scene gradCPT. Finally, we found associations between brain activity and behavioral attentional responses. ConclusionThis study gives a better understanding of the neural correlates of sustained attention and inhibition in a typically developing adolescent population.

Speech and language therapy can be an effective tool in improving language in post-stroke aphasia. Despite an increasing literature on the efficacy of language therapies, there is a dearth of evidence about the neurocognitive mechanisms that underpin language re-learning, including the mechanisms implicated in neurotypical learning. Neurotypical word acquisition fits within the idea of Complementary Learning Systems, whereby an episodic hippocampal system supports initial rapid and sparse learning, whilst longer-term consolidation and extraction of statistical regularities across items is underpinned by neocortical systems. Therapy may drive these neurotypical learning mechanisms, and efficacy outcome may depend on whether there is available spared tissue across these dual systems to support learning. Here, for the first time, we utilised a reverse translation approach to explore these learning mechanisms in post-stroke aphasia, spanning a continuum of consolidation success. After three weeks of daily anomia treatment, 16 patients completed a functional magnetic resonance imaging protocol; a picture naming task which probed (i) premorbid vocabulary retained despite aphasia, (ii) newly re-learned treated items and (iii) untreated/unknown and therefore unconsolidated items. The treatment was successful, significantly improving patients naming accuracy and reaction time post-treatment. Consistent with the Complementary Learning Systems hypothesis, patients overall naming of treated items, like that of controls when learning new vocabulary, was associated with increased activation of both episodic and language regions. Patients with relatively preserved left hemisphere language regions, aligned with the control data in that hippocampal activity during naming of treated items was associated with lower accuracy and slower responses - demonstrating the shifting division of labour from hippocampally-dependent new learning towards cortical support for the efficiently-named consolidated items. In contrast, patients with greater damage to the left inferior frontal gyrus displayed the opposite pattern (greater hippocampal activity when naming treated items was associated with quicker responses), implying that their therapy-driven learning was still wholly hippocampally reliant. Open accessFor the purpose of open access, the UKRI-funded authors have applied a Creative Commons Attribution (CC-BY) licence to any Author Accepted Manuscript version arising from this submission.

The absence of visual mental imagery, called aphantasia, occurs congenitally in up to 3% of the general population, but the brain regions responsible for aphantasia remain uncertain. Rare cases of acquired aphantasia caused by brain lesions may lend insight into the neuroanatomy responsible for this condition, and the neural substrate of visual mental imagery itself. We performed a systematic literature review to identify cases of lesion-induced aphantasia and traced the lesion locations onto a common brain atlas. These locations were compared to control lesions causing other neuropsychiatric symptoms (n = 887). First, we tested for intersection between lesion locations and an a priori region of interest termed the fusiform imagery node, active during visual mental imagery tasks. Second, we tested for connectivity between lesion locations and this region of interest, leveraging resting-state functional connectivity from a large cohort of healthy subjects (n = 1000). Finally, we performed a data-driven analysis assessing whole-brain lesion connectivity that was sensitive (100 % overlap) and specific (family-wise error p < 0.05) for aphantasia. We identified 12 cases of lesion-induced aphantasia, only 5 of which intersected the fusiform imagery node. However, 100% of these lesion locations were functionally connected to the fusiform imagery node. Connectivity to this region was both sensitive (100% overlap) and specific (family-wise error p<0.05) for aphantasia in a data-driven whole-brain analysis. Lesions causing acquired aphantasia occur in multiple different brain regions but are all functionally connected to the left fusiform imagery node. This study provides causal support for the importance of this brain region in visual mental imagery.

AimCerebral Visual Impairment (CVI), an underdiagnosed cause of childhood visual impairment, presents heterogeneous symptoms involving varying degrees of dorsal and ventral stream dysfunction. We investigated whether impaired reach-to-grasp integration occurs in CVI as a potential marker of dorsal stream dysfunction. MethodPeople with CVI (children aged 7-17, n = 16; adults aged 18-25, n = 6) and control participants (children, n = 14; adults, n = 10) reached with their left hand to grasp plastic blocks with and without a blindfold. Reach-to-grasp timing and hand shaping measures were assessed using frame-by-frame video analysis. ResultsEven when they could see the block, people with CVI displayed prolonged grasp relative to reach durations, more static hand shaping during the reach, and increased reliance on non-visual hand shaping strategies after block contact to secure final grasp. The three measures were incorporated into a single composite Reach-to-Grasp Integration (RGI) score that distinguished people with CVI from controls. InterpretationTemporal, sensory, and functional dissociation of the reach and grasp occurs in CVI, consistent with dorsal stream dysfunction, and is captured by the RGI score. The RGI score could form the basis for CVI behavioural screening tools beyond standard visual assessments. What this paper addsO_LIPeople with CVI display impaired visually-guided integration of the reach and grasp, consistent with dorsal stream dysfunction. C_LIO_LIPeople with CVI use static preplanned hand shapes during visually-guided reaching. C_LIO_LIPeople with CVI rely on non-visual hand shaping strategies after target contact to facilitate grasping. C_LIO_LIThe composite Reach-to-Grasp Integration (RGI) score distinguishes CVI from control children and adults. C_LI

BackgroundApproximately 1 in 4 children who sustain an acquired brain injury (ABI) have attention difficulties impacting education, employment, and community participation. These difficulties arise from dysfunction in attention-related brain networks, incentivising the use of transcranial direct current stimulation (tDCS). Objective/HypothesisWe investigated whether a single tDCS session improved attention following childhood ABI and whether baseline structural connectivity (sc), functional connectivity (fc), attention, and/or simulated electric fields (E-field) explained variability in response. MethodsIn a randomised, single-blind, within-subject, sham-controlled trial, 15 children with ABI (mean 12.7 years) and 15 healthy controls (HCs) received three single tDCS sessions (1mA dorsolateral prefrontal cortex [dlPFC], 1mA inferior frontal gyrus [IFG], sham; 20min) during gamified attention training. We examined post-intervention changes in attention according to flanker and stop signal reaction time (RT). We used multi-modal analyses (high-density electroencephalography [HD-EEG], diffusion tensor imaging, magnetic resonance imaging) to investigate inter-individual variability in tDCS response, according to associations between RT change and baseline fc, sc, attention, and E-fields. ResultsAlthough no effect of active versus sham tDCS was found overall, participants with lower theta or higher gamma default mode network connectivity and poorer attention at baseline showed greater response to tDCS. Higher E-fields were associated with greater response. No serious adverse effects occurred. ConclusionsA single tDCS session targeting dlPFC or IFG did not improve attention following pediatric ABI. We demonstrated how HD-EEG source-based connectivity may be used to personalise tDCS. Future research should explore whether personalization, and/or repeated tDCS sessions can improve attention following pediatric ABI.

ObjectiveAlongside objective performance declines, self-reported cognitive symptoms after traumatic brain injury (TBI) abound. Mental fog is one symptom that has been underexplored. The current project investigated mental fog across two studies of individuals with mild traumatic brain injury and moderate-to-severe traumatic brain injury to close our knowledge gap about differences in severity. We then explored the cognitive and affective correlates of mental fog within these groups. MethodsUsing between-groups designs, the first study recruited individuals with acute mild TBI (n = 15) along with a healthy control group (n = 16). Simultaneously, a second study recruited persons with post-acute moderate-to-severe TBI, a stage when self-reports are most reliable (n = 15). Measures across the studies were harmonized and involved measuring mental fog (Mental Clutter Scale), objective cognition (Cogstate(R) and UFOV(R)), and depressive symptoms. In addition to descriptive group difference analyses, nonparametric correlations determined associations between mental fog, objective cognition, and depressive symptoms. ResultsResults revealed higher self-reported mental fog in acute mild TBI compared to healthy controls. And though exploratory, post-acute moderate-to-severe TBI also appears characterized by greater mental fog. Correlations showed that mental fog in mild TBI corresponded to greater depressive symptoms (r = .66) but was unrelated to objective cognition. By contrast, mental fog in moderate-to-severe TBI corresponded to poorer working memory (r = .68) and slowed processing speed (r = -.55) but was unrelated to depressive symptoms. ConclusionAs a common symptom in TBI, mental fog distinguishes individuals with acute mild TBI from uninjured peers. Mental fog also appears to reflect challenges in recovery, including depressive symptoms and objective cognitive problems. Screening for mental fog, in addition to other cognitive symptoms, might be worthwhile in these populations.

PurposeBrain imaging has provided puzzle pieces in the understanding of language. In neurologically healthy populations, structure of certain brain regions is associated with particular language functions (e.g., semantics, phonology). In studies on focal brain damage, certain brain regions or connections are considered sufficient or necessary for a given language function. However, few of these account for the effects of lesioned tissue on the functional dynamics of the brain for language processing. Here, functional connectivity amongst semantic-phonologic regions of interest (ROIs) is assessed to fill a gap in our understanding about the neural substrates of impaired language and whether connectivity strength can predict language performance on a clinical tool in individuals with aphasia. MethodClinical assessment of language, using the Western Aphasia Battery-Revised (WAB-R), and resting-state fMRI data were obtained for 30 individuals with chronic aphasia secondary to left hemisphere stroke and 18 age-matched healthy controls. Functional connectivity (FC) between bilateral ROIs was contrasted by group and used to predict WAB-R scores. ResultsNetwork coherence was observed in healthy controls and participants with stroke. The left-right premotor cortex connection was stronger in healthy controls, as reported by New et al. (2015) in the same data set. FC of (1) bilateral connections between temporal regions, in the left hemisphere and bilaterally, predicted lexical semantic processing for Auditory Comprehension and (2) ipsilateral connections between temporal and frontal regions in both hemispheres predicted access to semantic-phonologic representations and processing for verbal production. ConclusionsNetwork connectivity of brain regions associated with semantic-phonologic processing is predictive of language performance in post-stroke aphasia. The most predictive connections involved right hemisphere ROIs - particularly those for which structural adaptions are known to associate with recovered word retrieval performance. Predictions may be made, based on these findings, about which connections have potential as targets for neuroplastic functional changes with intervention in aphasia.

Reading proficiency is essential for everyday life, with the Visual Word Form Area (VWFA) of the brains reading network playing a key role in fluent reading. Reduced VWFA activation has been linked to impaired reading. Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback allows individuals to learn to regulate brain activity in targeted brain areas. While our previous study demonstrated the feasibility of VWFA regulation in adults with typical reading skills, this study investigated whether adults with poor reading skills could similarly upregulate VWFA activity using rt-fMRI neurofeedback. Participants with typical (n = 20) and poor (n = 19) reading skills were trained to upregulate their VWFA activity during six runs of rt-fMRI neurofeedback training. Before and after training, no-feedback runs were conducted where the same regulation task had to be performed without receiving feedback. Feedback on activation was provided based on each participants individually defined VWFA, determined through a functional localizer task. Our study yielded two key findings: First, upregulation of the VWFA through rt-fMRI neurofeedback can be learned irrespective of an individuals reading proficiency. Even participants with poor reading skills, who exhibited lower VWFA activation and employed fewer reading-related mental strategies, achieved upregulation of this region through neurofeedback. Second, upregulating the VWFA through rt-fMRI neurofeedback resulted in increased VWFA activity after training, even without feedback, compared to pre-training in both adults with typical and poor reading skills. Overall, the feasibility of regulating VWFA activity, regardless of reading skills, provides a promising foundation for developing brain-based interventions to address reading impairments through rt-fMRI-based regulation training.

IntroductionCognitive impairments are prevalent in many neurological disorders and remain underdiagnosed and poorly studied longitudinally. Unsupervised remote cognitive testing is an accessible, scalable, and cost-effective solution, however it often fails to separate cognitive deficits from commonly co-occurring motor impairments. To address this gap, we present a computational framework that isolates cognitive ability from motor impairment in self-administered digital tasks. MethodsStroke was chosen as a representative neurological disorder, as patients frequently experience both motor and cognitive impairments. Our validation analyses spanned 18 computerised tasks completed by 171 patients longitudinally, covering a broad spectrum of cognitive and motor domains. The computational model was applied on trial-level data to disentangle the contribution of motor and cognitive processes. ResultsIn patients with motor hand impairment, standard accuracy performance metrics were confounded in 6 tasks (p<.05, FDR-corrected). In contrast, the Modelled Cognitive metrics obtained from the computational framework showed no significant effects of impaired hand (p>.05, FDR-corrected). Moreover, the Modelled Cognitive metrics correlated more strongly with clinical pen-and-paper scales (mean R2=0.64 vs. 0.43) and functional outcomes (mean R2=0.16 vs 0.09). Brain-behaviour associations were stronger when using the Modelled Cognitive metrics, and revealed intuitive multivariate relationships with individual tasks. InterpretationWe present converging evidence for the improved clinical utility and validity of the Modelled Cognitive metrics within neurological conditions characterised by co-occurring motor and cognitive deficits. Addressing the confounding effect of motor impairments improves the reliability and biological validity of self-administered digital assessments, enhances accessibility, and supports early detection and intervention across neurological disorders. FundingThis research is funded by the UK Medical Research Council (MR/T001402/1).

The relationship between symbolic thinking and language abilities is a topic of intense debate. We have recently discovered three distinct phenotypes of language comprehension, which we defined as command, modifier and syntactic phenotypes (Vyshedskiy et al., 2024). Individuals in the command phenotype were limited to comprehension of simple commands, while those in the modifier phenotype showed additional comprehension of color, size, and number modifiers. Finally, individuals in the most-advanced syntactic phenotype added comprehension of spatial prepositions, verb tenses, flexible syntax, possessive pronouns, complex explanations, and fairytales. In this report we analyzed how these three language phenotypes differed in their symbolic thinking as exhibited through their drawing abilities. In a cohort of 39,654 autistic individuals 4- to 21-years-of-age, parents reported that drawing, coloring and art was manifested by 36.0% of participants. Among these individuals, representational drawing was manifested by 54.1% of individuals with syntactic-, 27.7% of those with modifier-, and 10.1% of those with command-phenotype (all pairwise differences between the phenotypes were statistically significant, p < 0.0001). The ability to draw a novel image per parents description (e.g. a three-headed horse) was reported by 34.6% of individuals with syntactic-, 7.9% of those with modifier-, and 1.9% of individuals with command-phenotype (all pairwise differences between the phenotypes were statistically significant, p < 0.0001). These results show strong association between the representational drawing ability and the syntactic-language-comprehension-phenotype, suggesting a potential benefit of drawing interventions in language therapy.

Recently we proposed and tested a novel framework based on information theory about the features of agrammatism in patients with the nonfluent variant of primary progressive aphasia (nfvPPA). These features include short sentences, simplified structures, the omission of function words, reduced use of verbs, and increased use of heavy verbs. After distinguishing the syntactic and lexical features of agrammatism, we proposed that the lexical features are not defects but rather a compensatory response to structural deficits. We showed that although patients with nfvPPA have difficulty using complex structures, they use more informative words to facilitate the transfer of their intended message. In this work, we demonstrated the generalizability of our findings to patients with Brocas aphasia who share similar neuroanatomical involvements with patients with nfvPPA. We found that patients with Brocas aphasia use simpler syntactic structures as measured by higher syntax frequency. We also found that the use of simpler syntax predicts the use of lower-frequency words. Furthermore, our study showed that producing sentences of lower word frequency is likely achieved through the canonical features of agrammatism, i.e., higher proportions of content words over function words, nouns over verbs, and heavy verbs over light verbs.

ImportanceDevelopmental dyslexia (dyslexia) is a genetic-based learning disorder affecting 7-10% of the general population and has detrimental impacts on mental health and vocational potential. Individuals with dyslexia show altered functional organization of the language and reading neural networks; however, it remains unknown how early these neural network alterations emerge in association with familial(genetic) vulnerability to dyslexia. ObjectiveTo determine whether the early development of large-scale neural functional connectivity is altered as a function of familial risk for dyslexia. DesignThis cohort study included 98 infants with (FHD+) and without (FHD-) a familial history of dyslexia recruited at Boston Childrens Hospital (BCH) between May 2011 and February 2019. SettingParticipants underwent structural and resting-state functional magnetic resonance imaging in the Department of Pediatric Radiology at BCH. ParticipantsFHD+ infants were defined as having at least one first-degree relative with dyslexia or reading difficulties and infants without familial risk for dyslexia (i.e., FHD-) were controls. Main outcomes and measuresWhole-brain functional connectivity patterns associated with 20 pre-defined cerebral regions important for long-term language and reading development were computed for each infant. Multivariate pattern analyses were applied to identify specific functional connectivity patterns that differentiated between FHD+ and FHD-infants. ResultsThe final sample consisted of 35 FHD+ (8.9 {+/-} 2.4 months, 15 females) and 63 FHD- (8.3 {+/-} 2.3 months, 36 females) infants. Multivariate pattern analyses identified distinctive functional connectivity patterns between the FHD+ and FHD-infants in the left fusiform gyrus (LFFG: accuracy = 0.55, pcorrected < 0.001, effect size: Cohens d = 0.76, 99% CI of the classification performance (classification accuracy-chance level) = [0.046, 0.062]). Moreover, the top five connections with greatest contribution to the classification performance connected LFFG with the frontal and temporoparietal regions of the language network. Conclusion and relevanceThe current study demonstrates that familial vulnerability to dyslexia is associated with an early onset of atypical functional connectivity of regions important for subsequent word form recognition during reading acquisition. Longitudinal studies linking the atypical functional network and school-age reading x(dis)abilities will be essential for further elucidating the ontogenetic mechanisms underlying the development of dyslexia. Key PointsO_ST_ABSQuestionC_ST_ABSAre functional topologies of language and reading-related regions in infancy associated with familial vulnerability to developmental dyslexia? FindingsIn a cohort study examining the resting-state functional connectivity of 98 infants during natural sleep, distinctive functional connectivity patterns of the left fusiform gyrus were observed between infants with and without a familial risk for dyslexia. These differences were evident despite comparable behavioral and socio-economic/environmental characteristics between the two groups. MeaningFamilial vulnerability of dyslexia is associated with early alterations in the infant functional connectivity of key regions important for subsequent word recognition, suggesting an atypical neural scaffold for reading acquisition.

ObjectiveTo assess overlap and uniqueness of established behavioral markers of speed of processing for different aspects of visual information within a cerebrovascular disease cohort, and to examine the link between these speed of processing markers and functional behavior, specifically walking. MethodsA cohort of 161 participants with cerebrovascular disease recruited to the Ontario Neurodegenerative Disease Research Initiative (ONDRI) were examined with three types of assessments: neuropsychology, saccadic eye movement and gait. Principal component analysis (PCA) and canonical correlation analysis (CCA) were performed on select variables from these assessments to reveal commonalities and discrepancies among the measures. ResultsPCA analysis revealed different variable patterns between neuropsychology and saccade assessments, with the first component characterized primarily by neuropsychology, and the second and third components more influenced by the saccade assessments. CCA analysis did not reveal association between different types of assessments with the exception of a modest, but significant, positive association between speed of processing measures from the neuropsychological assessments and gait speed. DiscussionNeuropsychological tests and the pro-saccade task can be used for assessment of speed of processing for two major features of visual information, visual perception vs. spatial location. Despite a general lack of association between different types of assessments, combining gait speed as an important contributor to the models reinforces the idea of the link between speed of processing and complex function such as walking, and provides support for the importance of attending to the potential consequences of changes in speed of processing after neurologic injury.

Two-thirds of the worlds 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. MethodsSeventy-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. ResultsParticipants 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. DiscussionLexical 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.