SOCOSCA
This project aims to deepen our understanding of the role of the cerebellum in social cognition and social-emotional behavior, by studying patients with autosomal dominant spinocerebellar ataxias (SCA). The cerebellum, long associated with motor skills, is now recognized for its cognitive and emotional functions. Using advanced neuroimaging techniques and comprehensive neuropsychological assessment, we hope to characterize social-cognitive deficits in SCA and identify structural and functional abnormalities of the cerebellum. This multidisciplinary project could lead to non-pharmacological clinical interventions and offer psycho-educational support to patients and their families, filling an important gap in the management of ACS.
Project background
The role of the cerebellum has evolved beyond motor function in recent decades. Research indicates that damage to the cognitive and limbic parts of the cerebellum, such as the posterior lobe (lobules VI/Crus I, Crus II/VIIB, lobules IX/X), leads to cerebellar cognitive and affective syndrome (CCAS). This syndrome includes deficits in executive functions, language processing, spatial cognition and emotion regulation. In addition, the cerebellum appears to play a role in social cognition, including emotion recognition and theory of mind. Clinical studies on patients with cerebellar lesions have confirmed deficits in these areas, marking the affective component of CCAS. Neuroimaging research has revealed that neural circuits in the cerebellum include connections with fronto-limbic regions, the amygdala, the insula, as well as the temporal, parietal and frontal cortices. The cerebellum participates in associative and paralimbic networks, and is integrated into executive control, mentalization and emotional systems. Despite these advances, the precise role of the cerebellum in social cognition still requires in-depth study in healthy subjects and patients with social deficits due to cerebellar lesions. Spinocerebellar ataxias (SCAs), dominant genetic diseases, result from degeneration of cerebellar connections. Cerebellar atrophy is common in several SCA subtypes (SCA 1, 2, 3, 6, 7), with specific degeneration of the posterior lobe. These conditions provide a solid basis for exploring the role of the cerebellum in social cognitive functioning.
Project objective and relevance
Therefore, by studying patients with autosomal dominant ACS, our aims are threefold:
- To characterize social-cognitive deficits in autosomal dominant ACS.
- To analyze cerebellar structural and functional abnormalities and cerebellar-cerebral networks, and their relationship to social-cognitive deficits.
- Examine the impact of these deficits on sociobehavioral regulation in SCA, particularly the affective component of CCAS.
We also plan to:
- To observe alterations in social-cognitive tasks in ACS patients compared to matched healthy controls, with distinct profiles according to subtypes.
- Establish links between social-cognitive deficits and affective dysfunction.
- To explore how specific cerebellar atrophy and circuit disruptions influence cognitive and affective deficits in SCA, as observed in other disorders.
Approach
We will study 120 French-speaking participants over 4 years: 80 adult patients with autosomal dominant ACS (ACS1, 2, 3, 6, 7) and 40 matched healthy controls. Our protocol is divided into two axes:
- Neuropsychological assessment: We will use standard tasks and ecological research methods to assess cognitive and affective components of social cognition, as well as non-social tasks to compare observed effects.
- Neuroimaging: We will use structural MRI (VBM), functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) tractography to study cerebellar morphometry, cerebellocerebral connectivity and networks associated with social deficits.
Expected results
This multidisciplinary project offers several perspectives.
- Neuroanatomical : Using innovative neuroimaging and neurocognitive protocols, this project will shed light on the neuroanatomical basis of socio-cognitive and socio-behavioral alterations in SCA. It will provide new insights into the role of the cerebellum and its connections in social cognition and human behavior.
- Clinical : This project could identify targets for non-pharmacological interventions aimed at the social dysfunctions of ACS patients. The literature suggests interventions targeting :
- Specifically one or more domains of social cognition (SC).
- SC as a whole.
- Skills that influence SC.
Academic and industrial partners from France and abroad
Scientific coordinator: Philippe Allain, Professor of Neuropsychology at the University of Angers (UA) and neuropsychologist (UHA), heads the Laboratoire de Psychologie des Pays de Loire (LPPL). He oversees meetings, protocol monitoring, and publication of results.
Consortium :
- Partner 1: LPPL specialists in cognitive neuroscience and clinical neuropsychology (P. Allain, J. Besnard). They define the cognitive and socio-cognitive assessment battery.
- Partner 2: Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS, UA), experts in medical image acquisition and analysis (M. Dinomais, M. Labriffe, J.B. Fasquel, P. Ali).
- Partner 3: IMT Atlantique (Brest campus), specialists in biophysical modeling and medical imaging (F. Rousseau).
- Partner 4: RCRND, neurologists and geneticist securing ACS patient recruitment and brain measurements (C. Verny, V. Pichon, C. Scherer-Gagou, A. Prundean, D. Bonneau).
Next steps
Study implementation and subject recruitment will be carried out in Year 1. Year 2 and Year 3 will be devoted to data collection, while Year 4 will be devoted to:
- Analysis of neuropsychological and neuroimaging data;
- Dissemination of results (publications, conferences, thesis defense).
With regard to risk management, given that the inclusion of participants is subject to prior approval by the Comité de Protection des Personnes (CPP), we plan to carry out this project over a 4-year period. This period will also enable us to recruit a sufficient number of patients at UHA. This represents a cohort of 80 eligible patients. Based on our previous experience with advanced neuroimaging studies [functional MRI, VBM, DTI; 40, 41, 42], all MRI scans will be performed on the same MRI scanner (3 T, Siemens). This will ensure consistency in the acquisition of the MRI protocol.