Background: Diagnostic reasoning involves the thinking steps up to and including arrival at a diagnosis. Dual process theory posits that a physician’s thinking is based on both non-analytic or fast, subconscious thinking and analytic thinking that is slower, more conscious, effortful and characterized by comparing and contrasting alternatives. Expertise in clinical reasoning may relate to the two dimensions measured by the diagnostic thinking inventory (DTI): memory structure and flexibility in thinking. Aim: Explored the functional magnetic resonance imaging (fMRI) correlates of these two aspects of the DTI: memory structure and flexibility of thinking. Methods: Participants answered and reflected upon multiple-choice questions (MCQs) during fMRI. A DTI was completed shortly after the scan. The brain processes associated with the two dimensions of the DTI were correlated with fMRI phases – assessing flexibility in thinking during analytical clinical reasoning, memory structure during non-analytical clinical reasoning and the total DTI during both non-analytical and analytical reasoning in experienced physicians. Results: Each DTI component was associated with distinct functional neuroanatomic activation patterns, particularly in the prefrontal cortex. Conclusion: Our findings support diagnostic thinking conceptual models and indicate mechanisms through which cognitive demands may induce functional adaptation within the prefrontal cortex. This provides additional objective validity evidence for the use of the DTI in medical education and practice settings.