Ethical and practical considerations in managing incidental findings in functional magnetic resonance imaging

Abstract

Functional magnetic resonance imaging has emerged as a powerful tool for mapping the neurologic underpinnings of sensory, motor and cognitive function. Much of this evolution carries assumptions about the subject population under study and, in particular, the neurologic status of subjects entered into studies either as healthy controls or as belonging to a specific disease group. Recent reports of incidental MRI abnormalities in normal volunteers for fMRI studies have brought to attention a variety of practical challenges and ethical dilemmas for researchers, many of whom are not physicians and most of whom have no formal radiological training. We propose a minimum standard for consenting subjects in fMRI protocols, and consider strategies over the longer term that call for expert physician participation, archiving of incidental findings including false positives, and the adoption of guidelines for handling variation in neural activations or performance that appear outside expected norms.

Introduction

Over the past decade, functional magnetic resonance imaging (fMRI) has emerged as a powerful tool for mapping sensory, motor and cognitive function, and has reaffirmed and expanded upon clinical neurologic and neuropsychological studies, and neuroimaging studies based on other modalities such as electroencephalography (EEG), positron emission tomography (PET), single photon emission tomography (SPECT), and magnetoencephalography (MEG). Several recent fMRI studies have even begun to elucidate the mechanisms of complex and abstract phenomena such as decision-making and moral behavior. Using event-related fMRI, for example, Van Veen, Cohen, Botvinick, Stenger, and Carter (2001) have demonstrated a highly specific contribution of the anterior cingulate cortex to executive functions at response-related levels of processing; and, in a series of fMRI studies using moral dilemmas as stimuli, Greene, Sommerville, Nystrom, Darley, and Cohen (2001) have probed the influence of variations in emotional engagement on moral judgment. Thus, in this second decade of functional neuroimaging with MRI, it has become possible to detect an alignment of neural activation with some of the highest forms of human cognition; new perspectives and moral questions about rational thinking, intention, and individuality are certain to follow. Much of our thinking from neuroimaging studies, however, carries assumptions or presumptions about the subject population under study and, in particular, the neurologic status of subjects entered into studies as either healthy controls or belonging to a specific neurologic disease group. Despite reports of unexpected MRI findings in clinical and research brain imaging in both adult and pediatric cohorts (e.g., Illes, Kim, Kaplan, Reiss, & Atlas, 2002; Katzman, Dagher, & Patronas, 1999; Kim, Illes, Kaplan, Reiss, & Atlas, 2002) many, if not most, research fMRI studies involving volunteers are performed by non-physicians; unanticipated findings on these imaging studies may go unrecognized and thereby leave subjects without appropriate referral.

The detection, significance, and management of incidental findings are keys to the welfare of the research subject as well as to the integrity of the studies. We will focus on both of these issues here and consider short-term and long-term strategies involving informed consent, expert physician participation, archiving of incidental findings, and the adoption of guidelines for handling unusual variation in neural activations or performance as a first step in a call for debate and consensus in the fMRI community to address these issues.