Periodic Reporting for period 1 - MapInCSC (Mapping the Interaction between Semantic Representation and Control Systems: The Controlled Semantic Cognition)
Période du rapport: 2020-08-01 au 2022-07-31
This study focused on the challenge of how to relate behavioural dimensions to underlying neurological changes in patients. The study applied multidimensional behavioural geometries to represent the variations in patients' symptoms and relate them to atrophy patterns. Frontotemporal dementia (FTD) cortical and subcortical syndromes, characterised by progressive cognitive, behavioural, language, and motor deficits, were used as test cases. The investigation achieved this aim by 1) Using principal component analysis (PCA) to extract the multidimensional behavioural geometry from the Mini-Language State Examination (MLSE) battery, thereby capturing the continuum-graded language variations across the FTD spectrum. 2) Employing three approaches to reveal the brain-behaviour relationships: (i) classic univariate voxel-based morphometry correlations; (ii) PCA of atrophy maps to extract coherent brain patterns and thus test which of these disease-defined anatomical dimensions relate to the behavioural dimensions; and (iii) exploring whether variation on the behavioural dimensions relates to the integrity of one versus several brain regions, and thus shifting from univariate to multivariate regression models to capture the latter cognition-to-distributed network relationships, when they exist.
Our findings revealed more distributed atrophy patterns for motor-speech/phonology and syntax factors, while semantics is more localised in the anterior part of the inferior temporal lobe. Importantly, while many studies rely on univariate correlations to investigate brain correlations in cognitive disorders, our findings indicate that this approach falls short of capturing the complex relationships between behaviour and the brain. Given the distributed and interactive nature of language functions, isolating specific language processes in the brain poses a great challenge, affecting how language is altered, reflected in the heterogeneity of language deficits in FTD. Incorporating multivariate analysis becomes essential to capture these intricate associations and identify common and distinct neural mechanisms of language. In conclusion, other aspects of language besides semantics rely on various brain regions, demonstrating the complex multidimensional architecture of language functions.
An important aspect of my work has been sharing the results with the scientific community. I achieved this by presenting findings at scientific conferences (e.g. BNA2023 Neuroscience Festival, CLS annual symposium 2022, ISFTD 2022, CNS2022 - New Horizons, SNL 2020), preparing publications (two under review), presentations on internal and external meetings and collaborating with other fellows.
The impact of this project extends to my potential and future career prospects. The training and experience gained in transdiagnostic approaches position me at the forefront of innovative research methodologies in neurodegenerative disorders, opening up opportunities for collaboration and advancement. The MSCA fellowship has enhanced my management skills, making me a valuable asset in fostering research. Whether in my current role or future endeavours, I am well-prepared to drive scientific advancements and positively impact the field of neurodegenerative disorders.
From a socio-economic perspective, this work contributes to the innovation capacity in neurodegenerative disorders by improving understanding and diagnosis, leading to better patient care and management strategies. The research addresses the need for more accurate assessments of cognitive impairments, enabling tailored interventions and therapies, ultimately enhancing the quality of life for individuals affected by these disorders. Moreover, the project aligns with the priorities of European healthcare policies, advancing precision medicine and personalized healthcare. The results of this research are of great interest to various stakeholders, including healthcare professionals, researchers, and pharmaceutical companies specializing in neurodegenerative diseases.