Incidental findings in magnetic resonance imaging (MRI) brain research

The use of magnetic resonance imaging (MRI) to investigate brain structure ("structural MRI") and function (so-called "functional MRI") has become increasingly common among neuroscientists, psychologists, and even economists in recent years. Yet, despite this increase in use, relatively little attention has been paid to the issue of incidental findings. The current paper discusses these issues, and anticipates the future of incidental findings in the context of other neuroimaging tools currently being used to investigate the living brain.     

The Management of Incidental Findings in Neuro-Imaging Research: Framework and Recommendations

This paper addresses the question of how incidental findings (IFs) in clinical research should be managed by researchers, focusing in detail on IFs discovered in neuroimaging research. It begins by engaging the larger research ethics issue of whether researchers have any obligations of clinical care to participants, and assesses the content and merits of one particular framework for answering this question, Richardson and Belsky's ancillary care model. From here the paper develops an organizational structure for integrating the ancillary care model with existing research ethics standards, with the aim of better understanding their respective domains. It makes a distinction between incidental findings that are anticipated by informed consent documents, and those that are unanticipated, arguing that this distinction is critical for evaluating researcher obligations. Finally, it takes on the issue of incidental findings in neuroimaging research, translating the standards discussed into recommendations for both unanticipated and anticipated findings.     

Research malpractice and the issue of incidental findings.

Human subject research involving brain imaging is likely to reveal significant incidental findings of abnormal brain morphology. Because of this fact and because of the fiduciary relationship between researcher and subject, board-certified or board-eligible radiologists should review the scans to look for any abnormality, the scans should be conducted in accordance with standard medical practice for reviewing the clinical status of the whole brain, and the informed consent process should disclose the possibility that incidental findings may be revealed and what consequences will follow. In the event such findings are revealed, qualified physicians should explain to the subject the significance of the findings and the alternatives available.     

Incidental findings in human subjects research: what do investigators owe research participants?

The use of brain imaging technology as a common tool of research has spawned concern and debate over how investigators should respond to incidental findings discovered in the course of research. In this article, we argue that investigators have an obligation to respond to incidental findings in view of their entering into a professional relationship with research participants in which they are granted privileged access to private information with potential relevance to participants' health. We discuss the scope and limits of this professional obligation to respond to incidental findings, bearing in mind that the relationship between investigators and research participants differs fundamentally from the doctor-patient relationship.     

Understanding incidental findings in the context of genetics and genomics.

Human genetic and genomic research can yield information that may be of clinical relevance to the individuals who participate as subjects of the research. It has been common practice among researchers to notify participants during the informed consent process that no individual results will be disclosed, "incidental" or otherwise. However, as genetic information obtained in research becomes orders of magnitude more voluminous, increasingly accessible online, and more informative, this precedent may no longer be appropriate. There is not yet consensus on the responsibilities of researchers to disclose individual research results to research participants. Empirical research suggests that participants want to know individual research results. On the other hand, the increased resolution and power afforded by new genomic analyses may lead to findings of statistical, but not necessarily clinical, significance. This paper addresses the issues to be considered in deciding whether and how to disclose "incidental" findings or other findings of clinical significance that arise in the course of human genomic and genetic research. What research results should be offered, and what should not be offered? For which research should individual results be offered to research participants, when should they be offered, how, and to whom?     

Empirical analysis of current approaches to incidental findings

This paper presents results found through searching publicly available U.S. data sources for information about how to handle incidental findings (IF) in human subjects research, especially in genetics and genomics research, neuroimaging research, and CT colonography research. We searched the Web sites of 14 federal agencies, 22 professional societies, and 100 universities, as well as used the search engine Google for actual consent forms that had been posted on the Internet. Our analysis of these documents showed that there is very little public guidance available for researchers as to how to deal with incidental findings. Moreover, the guidance available is not consistent.     

The rise of neuroskepticism

The increasing popularity of functional neuroimaging technologies in multiple disciplines has gained attention from within and outside the field of neuroscience. As the scope of research employing functional neuroimaging technologies broadens, there appears to also be a growing concern about the use of these technologies and the related social, ethical and legal issues. These concerns have been coined 'neuroskepticism'. First, we review how the term neuroskepticism has been previously used and defined. Second, we examine review and commentary articles published in journals with top impact factors, probing the presence and evolution of neuroskepticism within these articles. Results demonstrate a wide, but expected, range of issues associated with functional neuroimaging. It also appears that neuroskepticism is increasing as functional neuroimaging technologies gain popularity, which may indicate the presence of a classic Gartner Hype Cycle.     

Update on Neuroimaging and Cognitive Functioning in Maltreatment-Related Pediatric PTSD: Treatment Implications

This article reviews maltreatment-related pediatric posttraumatic stress disorder (PTSD) neuroimaging and neuropsychology research. Existent interventions that target brain networks associated with PTSD and cognitive impairment are highlighted. Furthermore, the benefits of combining neuroimaging and neuropsychology research in treatment outcomes are discussed. To conduct this review, a literature search was done utilizing the words MRI, structural, functional, neuropsychological testing, children, maltreatment, treatment, and PTSD. This was supplemented with a direct search of developmental trauma experts. Results from the neuroimaging studies found differences in the total cerebral volume, prefrontal cortex, hippocampus, cerebellum, superior temporal gyrus, corpus callosum, and other regions in maltreatment-related childhood PTSD. Neuropsychological findings demonstrate deficits in memory, attention, learning, and executive function that correspond to these brain regions. Existent and novel psychotherapeutic interventions address these deficits. These interventions may be directed at key networks associated with cognitive processing. Future directions include the implementation of treatment outcome research integrating psychotherapy with putative biological and psychological markers.     

Bridging philosophical and practical implications of incidental findings in brain research

Empirical studies and ethical-legal analyses have demonstrated that incidental findings in the brain, most commonly vascular in origin, must be addressed in the current era of imaging research. The challenges, however, are substantial. The discovery and management of incidental findings vary, at minimum, by institutional setting, professional background of investigators, and the inherent differences between research and clinical protocols. In the context of human subjects protections, the challenges of disclosure of unexpected and potentially meaningful clinical information concern privacy and confidentiality, communication, and responsibility for follow-up. Risks, including a blurring of boundaries between research and clinical practice, must be weighed against the possible benefit to subjects and a moral duty to inform. Identification and examination of these challenges have been met by scientific interest and a robust, interdisciplinary response resulting in the pragmatic recommendations discussed here.     

Genomic research and incidental findings.

The Human Genome Project showed that there is significant genetic variation within the population. Current research is accumulating large databases that may reveal genetic variations associated with disease or health risks, even if not intended as part of the study design. These incidental findings create legal, ethical, and financial challenges for researchers. Current federal and international guidelines are not adequate. Plans for dealing with incidental findings need to be established in the study design and reviewed and approved by the Institutional Review Board.     

Incidental findings in genetics research using archived DNA

Despite calls by some commentators for disclosing incidental findings in genetics research, several factors weigh in favor of caution. The technology of genetics has the power to uncover a vast array of information. The most potent argument for restraint in disclosure is that much research is pursued without consent so that the individual participant may not know that research is being conducted at all. Often the work is done by investigators and at institutions with which the person has no prior contact. Past practice is also relevant; genetics researchers historically have chosen not to disclose incidental findings, of which misattributed paternity and pleiotropic alleles such as ApoE have been the most common. Many people choose not to have genetic tests when given a choice. It may be desirable to discuss the topic of incidental findings when consent for research is obtained, but given the risk of unwanted surprise when there has been no prior discussion, the potential utility of incidental findings should be very high before they are even offered to individuals.     

Incidental findings in pediatric research

The approach to incidental research findings in children emerges by considering the child-parent relationship and balancing divergent interests and preferences. Incidental findings with clear and proximate clinical importance should be disclosed to both. We recommend that particularly sensitive or private information (e.g., pregnancy or drug use) should be disclosed to the adolescent first, while particularly serious information (e.g., cancer) should first be disclosed to the parent. These approaches allow the researcher to form an alliance with one party prior to engaging the other. However, unlike clinical settings, where there may be presumptive expectations of confidentiality about sharing information within the family, in most research settings it is reasonable to plan to disclose such information to both parties. It is important to communicate this plan during the informed consent process separately to adolescents to avoid enrolling adolescents when sensitive incidental findings such as pregnancy and drug use may be detected. The approach to incidental findings without clear and proximate benefit is challenging. Researchers should plan more limited disclosure of such incidental findings for pediatric participants than for adult participants.     

Playing Devil's advocate†: The case against fMRI lie detection

The advent of functional neuroimaging raises the intriguing possibility that investigators might be able to determine (one day) whether an individual is lying or telling the truth, according to the activity of their brain. Ultimately, such techniques might be applied in the forensic sphere. However, the empirical data supporting this conjecture derive from a body of work that is still early on in its development. Hence, when invited to play ‘Devil's advocate’, the author is prompted to critique a pivotal weakness within the current literature. The latter comprises 16 peer‐reviewed functional magnetic resonance imaging studies purporting to describe the neural correlates of lying. Most have demonstrated greater activation of prefrontal regions while participants lie relative to when they tell the truth. Most have failed to detect areas where truthfulness elicits specific activation (consistent with the view that truthfulness constitutes a ‘baseline’ in human cognition and communication; while lying requires something more). However, there is a great deal of variation between the findings described and, crucially, there is an absence of replication by investigators of their own findings. Hence, basic issues of reliability need to be addressed before functional neuroimaging is applied to cases that matter in the ‘real world’.     

Neuroimaging in Mild Traumatic Brain Injury

Neuroimaging in mild traumatic brain injury (mTBI) is reviewed. While computed tomography remains the acute standard for neuroimaging of mTBI, it is only sensitive to gross abnormalities and is typically performed as a measure to rule out more serious and life-threatening injury. Magnetic resonance imaging (MRI), especially at field strength of 3.0 T, is the follow-up neuroimaging standard for assessing potential underlying structural injury to the brain. Several MRI sequences are particularly sensitive to subtle hemorrhagic lesions and signal abnormalities in white matter, sensitive enough to detect pathology when present in mTBI. Clinical correlation of neuropsychological outcome with neuroimaging findings is discussed along with the future potential for functional neuroimaging in evaluating the mTBI patient.     

Do Jurors “Know” What Isn’t So About Child Witnesses?

Are expert witnesses needed in child sexual abuse cases to educate jurors about children’s memory, suggestibility, and reactions to abuse, or do jurors already know what such experts could tell them? To cast light on this question, we surveyed jurors and jury-eligible college students and compared their beliefs with what is known via scientific research regarding children’s memory and ability to testify, reactions to interrogation, and reactions to sexual abuse. We also asked participants to infer results of four widely cited studies of children’s suggestibility. Participants’ beliefs were consistent with findings from research on some issues (e.g., that children can be led to claim that false events occurred) but diverged from the scientific consensus on other issues (e.g., whether children can remember painful events in infancy). Similarly, participants sometimes overestimated and sometimes underestimated the level of suggestibility observed in empirical studies. Individual differences in accuracy were related to participants’ gender, education and ethnicity, and there was considerable disagreement among participants on many questions. Implications of findings for the admissibility of expert testimony in child abuse cases are discussed.     

Methodological issues in marital violence research

Recent interest in all aspects of domestic violence has stimulated rapid proliferation of research and literature. Although the knowledge base has grown, what we don't know still far exceeds what we do know. Starting from nothing, initial research tended to “sweep with a wide broom” in an effort to develop direction. The absence of an accepted methodology produced wide sample and design variations and inconsistent findings. The urgent press for information promoted a desire to disseminate “facts” that may have been less than factually derived from research that may have originally been seen as pilot in nature. This paper discusses the methodological issues that may have contributed to some of the inconsistencies in the marital violence literature and makes suggestions for the design and interpretation of research.     

Posttraumatic Stress Disorder: Current Concepts and Controversies

The diagnosis of posttraumatic stress disorder (PTSD) sometimes is raised in compensation claims, in tort settings, and in other medical–legal settings. Accordingly, health-care and legal professionals working in these areas need to be familiar with the current findings and controversies concerning the disorder. The purpose of this article is twofold. First, we review the most important findings concerning the clinical features, etiology, and treatment of PTSD. Second, we examine six major controversies concerning the disorder that are relevant to psychologists and other medical–legal practitioners: (a) the issue of what qualifies as a traumatic stressor, (b) the question of whether traumatic stress causes brain damage, (c) the validity of the concept of delayed-onset PTSD, (d) the recovered memory controversy, (e) the question of whether PTSD can arise when the person has no memory of the trauma (e.g., due to concussion), and (f) issues concerning PTSD malingering. Throughout this article we offer recommendations for psychological and other medical–legal practice in relation to the evaluation of PTSD claims.     

Increased lung weight in fatal intoxications is not unique to opioid drugs

Fatal intoxications with opioids are known to be associated with an increased lung weight, as well as with brain and pulmonary edema and urinary retention. However, there is evidence to suggest that fatal intoxications with non-opioid substances are also associated with increased lung weight; however, the latter aspect has not been comprehensively analyzed. To determine to what extent opioid and non-opioid substances are associated with increased lung and brain weight, we studied these organs in cases where the cause of death was attributed to intoxication with a single agent. Using data from cases autopsied at the National Board of Forensic Medicine (NBFM) in Sweden from 2009 through 2019 where the cause of death was attributed to a single substance, we created models of combined lung weight and brain weight. The models used age and sex as predictors as well as nested varying effects for the specific intoxicant and category of intoxicant. Suicidal hanging with negative toxicology cases served as controls. The population majority was male among both intoxications (68%) and controls (83%). The most common single substance group was opioids. All tested substances were associated with heavier lungs than controls, with the largest effect in the opioid group. Our findings show that several substances are associated with increased lung weight and that among intoxication deaths there is no difference in expected brain weight between substances. Hence, heavy lungs, without a reasonable explanation, should prompt a broad toxicological screening.     

Institutional review board approaches to the incidental findings problem

Institutional Review Boards (IRBs) are confronted with new challenges in the face of expanding technologies while fulfilling their existing regulatory mandate to ensure that plans are in place to protect subjects and to inform them of risks and benefits of research participation. Existing regulations and guidance do not address the issue of incidental findings (IFs), thus leaving awareness of the issue and the application of ethical principles to IRB judgment alone. In order to assure that researchers are aware of the potential for IFs, IRBs must identify which studies are likely to identify IFs and establish what plans should be put into place prior to study initiation to assure the subjects are appropriately informed of the likelihood of IFs, how IFs will be communicated to subjects, and whether the burden of follow-up falls on the researchers or is the subject's responsibility.     

Managing incidental findings in human subjects research: analysis and recommendations.

No consensus yet exists on how to handle incidental findings (IFs) in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are findings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed.