fMRI working memory hypo-activations in schizophrenia come with a coupling deficit between arousal and cognition

Cognition has become a target for therapeutic intervention and favoring arousal could be a way to help patients. Working memory is an arousal dependent cognitive function. This study used functional MRI (fMRI) as a surrogate marker of working memory to evaluate the sensitivity of patients' hypoactive regions to arousal in a subpopulation of rehabilitated patients. Are hypoactive regions sensitive to arousal? Does the deficit result from arousal deficit or improper coupling with cognitive activity? Eighteen patients and matched controls were recruited. Participants performed a working memory task during combined electroencephalographic (EEG) and fMRI measurements. Cortical regions sensitive to arousal were defined as those which were inversely correlated with low EEG frequencies. Overlap between the arousal-sensitive and hypoactive regions was assessed by mutual information. Arousal-cognitive coupling was evaluated by the correlation between the arousal effect and the task effect. In the patient group, most hypoactive voxels were sensitive to arousal and corresponded to the prefronto-parietal network. But patients had no arousal deficit. Although arousal seems to improve cognitive activity in most of the patients' cortical areas, this coupling appears to be specifically disturbed in their hypoactive regions. In conclusion, although increasing arousal may help cognition, it may do so in an unspecific way.