Cognitive Biomarkers in the Clinic: Lessons From Presurgical fMRI.

SUMMARY: Cognitive biomarkers are vital and uniquely challenging clinical tools. There has been marked growth in neuroimaging-based cognitive biomarkers across the past 40 years with more in development (e.g., clinical cognitive EEG). The challenges involved in developing cognitive biomarkers and key milestones in their development are reviewed here using clinical functional MRI's evolution as a case study. It is argued that indexing cognition is uniquely challenging because it requires patients to consistently use specific cognitive processes, and it is difficult or impossible to independently verify this occurred. This limitation can be successfully managed through careful analysis of standardized protocols for acquisition and interpretation, and ensuring the clinical application of biomarkers integrates disciplines with complementary expertise. Factors beneficial to the adoption of a novel cognitive biomarker include a clinical need and inadequate alternatives. Key milestones in the development of functional MRI included (1) demonstration that its performance was equivalent to its predecessor; (2) demonstration it predicted a clinically meaningful outcome; and (3) the establishment of infrastructure for both its execution and billing. Review of functional MRI and its predecessors suggest a cycle whereby successful cognitive biomarkers are validated, experience widespread adoption and customization/fragmentation, go through a period of review, and finally are refined and standardized. Those applying future cognitive biomarkers in the clinic can avoid some of the failures of clinical functional MRI by defining the skills and disciplines the method requires and routinely evaluating patient outcomes.