Abstract

Background Pathophysiological inquiries into schizophrenia require a consideration of one of its most defining features: disorganization and impoverishment in verbal behavior. This feature, often captured using the term Formal Thought Disorder (FTD), still remains to be one of the most poorly understood and understudied dimensions of schizophrenia. In particular, the large-scale network level dysfunction that contributes to FTD remains obscure to date. Study Design In this narrative review, we consider the various challenges that need to be addressed for us to move towards mapping FTD (construct) to a brain network level account (circuit). Study Results The construct-to-circuit mapping goal is now becoming more plausible than it ever was, given the parallel advent of brain stimulation and the tools providing objective readouts of human speech. Notwithstanding this, several challenges remain to be overcome before we can decisively map the neural basis of FTD. We highlight the need for phenotype refinement, robust experimental designs, informed analytical choices, and present plausible targets in and beyond the Language Network for brain stimulation studies in FTD. Conclusions Developing a therapeutically beneficial pathophysiological model of FTD is a challenging endeavor, but holds the promise of improving interpersonal communication and reducing social disability in schizophrenia. Addressing the issues raised in this review will be a decisive step in this direction.