Biology subjects

Gonzalez Alam, T. R. d. J.

Publications and source records attributed to Gonzalez Alam, T. R. d. J..

4 recordsLinked to original sources

bioRxiv2026

Lesion-Gradient Mapping in Semantic Aphasia: Comparisons of Observed and Simulated Effects of Stroke on Connectivity Gradients

Post-stroke semantic aphasia is characterised by multimodal semantic deficits and reflects disruption of a distributed brain network spanning frontal and temporal regions. Connectivity gradients, which capture key dimensions of whole-brain variation in functional connectivity, offer a promising framework for understanding the global impact of stroke on brain function. This study investigated whether changes in connectivity gradients following stroke can explain semantic aphasia deficits. First, we evaluated whether lesion-location and lesion-load information from structural MRI could predict the gradient changes observed in resting-state fMRI, as a proof-of-principle analysis. Second, we tested whether simulated gradient changes predict the severity of semantic impairment. Results show that post-stroke gradient changes simulated from structural MRI are correlated with actual changes in resting-state fMRI, particularly for the principal gradient that separates unimodal and heteromodal regions. Semantic deficits were related to simulated connectivity changes along this gradient: left prefrontal areas involved in controlled semantic retrieval exhibited stronger connectivity to unimodal cortex in patients with more severe deficits. Semantic deficits also correlated with changes in the second gradient, which distinguishes visual and motor cortex. Particularly, the right parahippocampal gyrus, typically visually biased--showed reduced visual connectivity in more impaired patients. These results help explain controlled semantic retrieval deficits in semantic aphasia. More broadly, the findings suggest that functional connectivity gradients capture post-stroke reorganisation of global brain networks linked to cognitive impairment, and that these changes can be estimated from structural MRI alone, enhancing clinical utility of gradient-based approaches. HighlightsO_LIFunctional connectivity gradients explain the multimodal impairments in semantic aphasia from a dimensional perspective, using the unimodal-transmodal and motor-visual axes. C_LIO_LIPost-stroke functional changes are explored through alterations in connectivity gradient patterns. C_LIO_LICortical lesion information from structural MRI can be used to simulate changes in connectivity gradients, offering potential clinical relevance. C_LI

neuroscience↗

bioRxiv2026

Reorganisation of Functional Connectivity Gradients in Post-Stroke Aphasia

Aphasia after stroke arises from focal damage to language-relevant cortex but is accompanied by widespread alterations in functional connectivity. In 60 stroke survivors, we related principal component-derived language scores to both lesion location and stroke-related changes in resting-state functional organisation, combining structural lesion-symptom mapping with a gradient-based approach. Structural lesion-symptom mapping identifies which damaged regions are associated with specific language impairments but does not capture how surviving cortex is reconfigured within the brains large-scale architecture. In contrast, lesion-gradient mapping characterises whole-brain connectivity gradients - data-driven axes that summarise the principal patterns of variation in cortical connectivity - and quantifies how behavioural variation relates to displacement of structurally intact regions along these intrinsic axes. Stroke was associated with altered positioning of cortical regions along the gradient separating default mode and control networks. Notably, the position of the left inferior frontal gyrus along this axis predicted dissociable language outcomes: displacement toward default mode connectivity patterns was associated with better speech but poorer writing performance. This opposing behavioural profile suggests that inferior frontal cortex contributes to language through flexible large-scale coupling, with distinct coupling regimes differentially supporting spoken and written production. These findings indicate that gradient-based mapping provides a mechanistic link between focal tissue damage and distributed behavioural consequences by revealing systematic reorganisation of macroscale functional architecture beyond the lesion site.

neuroscience↗

bioRxiv2023

Default mode network shows distinct emotional and contextual responses yet common effects of retrieval demands across tasks

The default mode network (DMN) lies towards the heteromodal end of the principal gradient of intrinsic connectivity, maximally separated from sensory-motor cortex. It supports memory-based cognition, including the capacity to retrieve conceptual and evaluative information from sensory inputs, and to generate meaningful states internally; however, the functional organisation of DMN that can support these distinct modes of retrieval remains unclear. We used fMRI to examine whether activation within subsystems of DMN differed as a function of retrieval demands, or the type of information to be retrieved, or both. In a picture association task, participants retrieved two types of semantic features about contexts and emotions: in the generate phase, these associations were retrieved from a novel picture, while in a switch phase, participants retrieved a new association for the same image. Semantic context and emotion trials were associated with dissociable DMN subnetworks, indicating that a key dimension of DMN organisation relates to the type of information being accessed. The fronto-temporal and medial temporal DMN showed a preference for emotional and contextual associations, respectively. Relative to the generate phase, the switch phase recruited clusters closer to the heteromodal apex of the principal gradient - a cortical hierarchy separating unimodal and heteromodal regions. There were no differences in this effect between association types. Instead, memory switching was associated with a distinct subnetwork associated with controlled internal cognition. These findings delineate distinct patterns of DMN recruitment for different kinds of associations yet common responses across tasks that reflect retrieval demands. Key pointsO_LIRetrieval of contextual and emotional features relies on distinct default mode subnetworks. C_LIO_LINovelty of visual input has an equivalent effect across default mode subnetworks. C_LIO_LISecondary associations retrieved from re-presented pictures activate heteromodal end of the principal gradient. C_LI

neuroscience↗

bioRxiv2023

Individual word representations dissociate from linguistic context along a cortical unimodal to heteromodal gradient

Language comprehension involves multiple hierarchical processing stages across time, space, and levels of representation. When processing a word, the sensory input is transformed into increasingly abstract representations that need to be integrated with the linguistic context. Thus, language comprehension involves both input-driven as well as context-dependent processes. While neuroimaging research has traditionally focused on mapping individual brain regions to the distinct underlying processes, recent studies indicate that whole-brain distributed patterns of cortical activation might be highly relevant for cognitive functions, including language. One such pattern, based on resting-state connectivity, is the principal cortical gradient, which dissociates sensory from heteromodal brain regions. The present study investigated the extent to which this gradient provides an organizational principle underlying language function, using a multimodal neuroimaging dataset of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) recordings from 102 participants during sentence reading. We found that the brain response to individual representations of a word (word length, orthographic distance and word frequency), which reflect visual, orthographic, and lexical properties, gradually increases towards the sensory end of the gradient. Although these properties showed opposite effect directions in fMRI and MEG, their association with the sensory end of the gradient was consistent across both neuroimaging modalities. In contrast, MEG revealed that properties reflecting a words relation to its linguistic context (semantic similarity and position within the sentence) involve the heteromodal end of the gradient to a stronger extent. This dissociation between individual word and contextual properties was stable across earlier and later time windows during word presentation, indicating interactive processing of word representations and linguistic context at opposing ends of the principal gradient. To conclude, our findings indicate that the principal gradient underlies the organization of a range of linguistic representations while supporting a gradual distinction between context-independent and context-dependent representations. Furthermore, the gradient reveals convergent patterns across neuroimaging modalities (similar location along the gradient) in the presence of divergent responses (opposite effect directions).

neuroscience↗