Single cell resolution of neurodegeneration in Gaucher disease

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults, is characterized by a multisystem involvement. Cognitive involvement predominantly affecting frono-temporal functions is an established clinical feature in this disorder. Brain imaging and metabolic studies showed a predominant involvement of fronto-temporal regions in DM1 patients, yet correlation studies among these findings and neuropsychological data gave contrasting results. In order to contribute to clarify the relationship between the metabolic changes documented in the frontal cortex of DM1 patients and a related cognitive task, we applied the functional near-infrared spectroscopy (fNIRS) during the execution of a phonemic verbal fluency task (pVFT).We enrolled 29 consecutive right-handed DM1 patients and 30 controls. A 2-channel fNIRS imaging system was used to investigate changes in oxygenated [O2Hb] and deoxygenated [HHb] hemoglobin concentrations in the prefrontal cortex (PFC) during a pVFT. [O2Hb] and [HHb] baseline-corrected activation values were calculated (respectively [O2Hb]c and [HHb]c).In the control group [O2Hb] significantly increased and [HHb] significantly decreased during the pVFT, in the DM1 group no significant variation was found for both parameters revealing no activation of both PFCs during the task. On the other hand, in the DM1 sample, statistical analysis revealed a direct correlation between [O2Hb]c of the left PFC and the pVFT score, while no correlation was observed in the control group.Our study reveals that DM1 patients show prefrontal hypometabolism during a specific frontal cognitive task compared to controls. Moreover the rapid temporal discrimination of fNIRS allows revealing the correlation between the PFC hypometabolism and the cognitive performance in DM1 patients.fNIRS can be helpful to understand the functional correlates of the frontal cognitive impairment in DM1.