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Lamothe, C.

Publications and source records attributed to Lamothe, C..

3 recordsLinked to original sources

Molecular and spatial profiling identifies immune endotypes for the stratification of OA patients

Osteoarthritis (OA) is a prevalent and heterogeneous joint disease in which synovial inflammation drives structural progression and pain. Despite the recognized heterogeneity of OA, the cellular and molecular organization of synovial tissue remains poorly characterized and defining distinct histological and immune endotypes could guide precision medicine and therapeutic targeting. We show that histologically defined synovial pathotypes are conserved across independent cohorts and correspond to distinct molecular immune endotypes. Integration of bulk and spatial transcriptomics with proteomics revealed niche-specific gene and protein signatures, reflecting the anatomical and functional diversity of OA synovium. The lympho-myeloid pathotype was characterized by mature ectopic lymphoid structures containing CD21+CD23+ follicular dendritic cells, spatially organized T and B cell zones, and clonally expanded T and B cells with shared immune cell receptor motifs, consistent with local adaptive immune activity correlating with radiological joint damage. These findings highlight how immune organization and cellular composition shape OA pathogenesis and provide a framework for endotype-guided stratification and therapeutic targeting.

immunology↗

Sound offset responses become highly informative in the auditory cortex

The entire auditory system downstream of the cochlea features pronounced offset responses, which follow the termination of sounds. Because of their ubiquity, it is still an unsolved question whether offset responses are generated early in the auditory system and then propagated or recomputed at each processing stage. Here, we analysed large-scale sound responses datasets acquired in the cochlear nucleus, inferior colliculus, medial geniculate nucleus and auditory cortex of awake mice. All brain regions showed a significant proportion of offset responses often combined with onset and sustained responses in the same neuron. However, using population activity decoders, we observed that neural representations after the sound offset show a three-fold increase in sound encoding accuracy in the cortex relative to subcortical areas. This result indicates that cortical offsets encode a more precise short-term memory of the elapsed sound than subcortical offsets and that they likely result from specific computational steps. Key points summaryO_LIOffset responses are found throughout the central auditory system C_LIO_LIOffset responses are often combined to sustained and onset responses at all central auditory system stages C_LIO_LIOffset responses provide richer information about elapsed sounds in the auditory cortex C_LI

neuroscience↗

Reconstructing Voice Identity from Noninvasive Auditory Cortex Recordings

The cerebral processing of voice information is known to engage, in human as well as non-human primates, "temporal voice areas" (TVAs) that respond preferentially to conspecific vocalizations. However, how voice information is represented by neuronal populations in these areas, particularly speaker identity information, remains poorly understood. Here, we used a deep neural network (DNN) to generate a high-level, small-dimension representational space for voice identity--the voice latent space (VLS)--and examined its linear relation with cerebral activity via encoding, representational similarity, and decoding analyses. We find that the VLS maps onto fMRI measures of cerebral activity in response to tens of thousands of voice stimuli from hundreds of different speaker identities and better accounts for the representational geometry for speaker identity in the TVAs than in A1. Moreover, the VLS allowed TVA-based reconstructions of voice stimuli that preserved essential aspects of speaker identity as assessed by both machine classifiers and human listeners. These results indicate that the DNN-derived VLS provides high-level representations of voice identity information in the TVAs.

neuroscience↗