Deciphering Signals of Imaging Techniques based on an Old Paradigm of Energy Metabolism Could Lead to Misunderstanding of Brain Function

Abstract

The sequence of the enzymatic reactions of glycolysis, the first biochemical pathway to be elucidated, was revealed in 1940. Today, eighty-five years later, this pathway is still displayed in textbooks, academic courses and online platforms unchanged from its original representation, despite major discoveries that question its accuracy. The dogmatic division of the pathway into aerobic and anaerobic glycolysis, each producing a different end-product, pyruvate or lactate, respectively, a concept that has been debunked, is continuing to be taught and used unchanged. As a result, the term “aerobic glycolysis” continues to imply an inefficient energy production that ends with lactate, despite the presence of oxygen. Therefore, the reliance of modern imaging techniques, such as BOLD fMRI, on the original schematics of the glycolytic pathway for both diagnostic purposes and in studying the metabolic basis of neural activity, could lead to skewed or misinterpreted signals. Scientists, physicians, teachers and students alike are encouraged to consider the paradigm shift from the original concept of glycolysis, based on the discoveries of the past four decades. A few published studies that employed imaging techniques were reexamined here, while relying on the proposed shift, indicating that their original results were misinterpreted. Consequently, it is recommended that for a better understanding of brain function and disfunction both physicians and brain research scientists should consider glycolytic paradigm shift when employing brain imaging techniques and interpreting their signals.