Seeing the bigger picture: multimodal neuroimaging to investigate neuropsychiatric illnesses

After several decades of moderate pessimism about the enter prise of developing novel therapeutic interventions for neuropsychiatric disorders, there has been recent progress toward the use of new treatment methods. For example, there is good reason to be optimistic given the efficacy of ket amine administration and brain stimulation techniques in the context of patients with depression for whom the right treat ment has yet to be identified.1–4 However, despite this pro gress, there is still a long way to go, and our group posits that the use of magnetic resonance imaging (MRI) techniques may play an important role in the continuing development and refinement of therapeutic strategies. Though this has been a popu lar notion for some time, MRI based techniques that index measures of brain structure and function have often been criticized for their inability to be used as a clinically relevant biomarker for diagnosis, treat ment design, or the evaluation of treatment efficacy. At pres ent, the nosology across all neuropsychiatric illness subtypes is typically not defined by biomarkerbased criteria, but rather by clinical observations that are then used to create clinical definitions (e.g., patients with schizophrenia for whom the right treatment has yet to be identified). While it is tempting to search for a HbA1clike biomarker (used to diag nose diabetes) for the clinical staging, prognostication and prediction of illness onset for neuropsychiatric illnesses, it is noteworthy that neurobiological features may interact across indices describing genetics and brain circuits. In keeping with this ideology, most neuroimaging work can be charac terized as singlemodality studies: studies that investigate a single neuroimaging modality (e.g., structural MRI only) in a given sample at a single time point, despite possibly collect ing multiple contrasts. While these works are undoubtedly useful and help to build a picture of illness pathophysiology, multimodal studies, which assess multiple neuroimaging modalities in the same population, have the potential to pro vide more comprehensive data that may be analyzed to iden tify biomarkers. Notably, previous research has shown how both structural and functional MRI can be used as a means to refine brain stimulation approaches.5,6 Also, there is emerging consensus that neuropsychiatric disorders affect brain circuits and net works.7,8 Importantly, many of these discoveries have enabled the development of the therapeutic treatments described above. The purpose of this editorial is to argue that, increas ingly, we need to move away from singlemodality studies and move toward the integration of multiple modalities in the context of neuroimaging studies if we are to develop robust signatures of brain function and dysfunction that are indica tive of neuropsychiatric illness and its underlying complexity.