Judy Illes

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.

Neurocognitive enhancement: what can we do and what should we do?

Our growing ability to alter brain function can be used to enhance the mental processes of normal individuals as well as to treat mental dysfunction in people who are ill. The prospect of neurocognitive enhancement raises many issues about what is safe, fair and otherwise morally acceptable. This article resulted from a meeting on neurocognitive enhancement that was held by the authors. Our goal is to review the state of the art in neurocognitive enhancement, its attendant social and ethical problems, and the ways in which society can address these problems.

Managing Incidental Findings and Research Results in Genomic Research Involving Biobanks and Archived Data Sets

Biobanks and archived data sets collecting samples and data have become crucial engines of genetic and genomic research. Unresolved, however, is what responsibilities biobanks should shoulder to manage incidental findings and individual research results of potential health, reproductive, or personal importance to individual contributors (using “biobank” here to refer both to collections of samples and collections of data). This article reports recommendations from a 2-year project funded by the National Institutes of Health. We analyze the responsibilities involved in managing the return of incidental findings and individual research results in a biobank research system (primary research or collection sites, the biobank itself, and secondary research sites). We suggest that biobanks shoulder significant responsibility for seeing that the biobank research system addresses the return question explicitly. When reidentification of individual contributors is possible, the biobank should work to enable the biobank research system to discharge four core responsibilities to (1) clarify the criteria for evaluating findings and the roster of returnable findings, (2) analyze a particular finding in relation to this, (3) reidentify the individual contributor, and (4) recontact the contributor to offer the finding. We suggest that findings that are analytically valid, reveal an established and substantial risk of a serious health condition, and are clinically actionable should generally be offered to consenting contributors. This article specifies 10 concrete recommendations, addressing new biobanks as well as those already in existence.Genet Med 2012:14(4):361–384

Convergent cortical representation of semantic processing in bilinguals

This study examined whether semantic processes in two languages (English and Spanish) are mediated by a common neural system in fluent bilinguals who acquired their second language years after acquiring their first language. Functional magnetic resonance imaging was performed while bilingual participants made semantic and nonsemantic decisions about words in Spanish and English. There was greater activation for semantic relative to nonsemantic decisions in left and right frontal regions, with greater left frontal activation. The locations of activations were similar for both languages, and no differences were found when semantic decisions for English and Spanish words were compared directly. These results demonstrate a shared frontal lobe system for semantic analysis of the languages and are consistent with cognitive research on bilingualism indicating that the two languages of a bilingual person access a common semantic system.

fMRI in the public eye

The wide dissemination and expanding applications of functional MRI have not escaped the attention of the media or discussion in the wider public arena. From the bench to the bedside, this technology has introduced substantial ethical challenges. Are the boundaries of what it can and cannot achieve being communicated to the public? Are its limitations understood? And given the complexities that are inherent to neuroscience, are current avenues for communication adequate?

Memory lateralization in medial temporal lobe epilepsy assessed by functional MRI.

Summary:  Purpose: To determine the utility of functional magnetic resonance imaging (fMRI) in preoperative lateralization of memory function in patients with medial temporal lobe epilepsy (MTLE).

Imaging or Imagining? A Neuroethics Challenge Informed by Genetics

From a twenty-first century partnership between bioethics and neuroscience, the modern field of neuroethics is emerging, and technologies enabling functional neuroimaging with unprecedented sensitivity have brought new ethical, social and legal issues to the forefront. Some issues, akin to those surrounding modern genetics, raise critical questions regarding prediction of disease, privacy and identity. However, with new and still-evolving insights into our neurobiology and previously unquantifiable features of profoundly personal behaviors such as social attitude, value and moral agency, the difficulty of carefully and properly interpreting the relationship between brain findings and our own self-concept is unprecedented. Therefore, while the ethics of genetics provides a legitimate starting point—even a backbone—for tackling ethical issues in neuroimaging, they do not suffice. Drawing on recent neuroimaging findings and their plausible real-world applications, we argue that interpretation of neuroimaging data is a key epistemological and ethical challenge. This challenge is two-fold. First, at the scientific level, the sheer complexity of neuroscience research poses challenges for integration of knowledge and meaningful interpretation of data. Second, at the social and cultural level, we find that interpretations of imaging studies are bound by cultural and anthropological frameworks. In particular, the introduction of concepts of self and personhood in neuroimaging illustrates the interaction of interpretation levels and is a major reason why ethical reflection on genetics will only partially help settle neuroethical issues. Indeed, ethical interpretation of such findings will necessitate not only traditional bioethical input but also a wider perspective on the construction of scientific knowledge.

Event-related covariances during a bimanual visuomotor task. I. Methods and analysis of stimulus- and response-locked data☆☆☆

A new method that measures between-channel, event-related covariances (ERCs) from scalp-recorded brain signals has been developed. The method was applied to recordings of 26 EEG channels from 7 right-handed men performing a bimanual visuomotor judgment task that required fine motor control. Covariance and time-delay measures were derived from pairs of filtered, laplacian-derived, averaged wave forms, which were enhanced by rejection of outlying trials, in intervals spanning event-related potential components. Stimulus- and response-locked ERC patterns were consistent with functional neuroanatomical models of visual stimulus processing and response execution. In early post-stimulus intervals, ERC patterns differed according to the physical properties of the stimulus; in later intervals, the patterns differed according to the subjective interpretation of the stimulus. The response-locked ERC patterns suggested 4 major cortical generators for the voluntary fine motor control required by the task: motor, somesthetic, premotor and/or supplementary motor, and prefrontal. This new method may thus be an advancement toward characterizing, both spatially and temporally, functional cortical networks in the human brain responsible for perception and action.

Neurotalk: improving the communication of neuroscience research

There is increasing pressure for neuroscientists to communicate their research and the societal implications of their findings to the public. Communicating science is challenging, and the transformation of communication by digital and interactive media increases the complexity of the challenge. To facilitate dialogue with the public in this new media landscape, we suggest three courses of action for the neuroscience community: a cultural shift that explicitly recognizes and rewards public outreach, the identification and development of neuroscience communication experts, and ongoing empirical research on the public communication of neuroscience.

Neurolinguistic features of spontaneous language production dissociate three forms of neurodegenerative disease: Alzheimer's, Huntington's, and Parkinson's.

An analysis of the temporal (prospective) form (silent and filled hesitations, repetitions, incomplete phrases, context-related comments, interjections), syntactic form, and lexical (retrospective) form (verbal deviations, open and closed class phrases) of spontaneous language production of early and middle stage Alzheimers, Huntingtons, and Parkinsons patients was made. Results showed that the language structure was disrupted in each disease, but in different ways. Temporal interruptions of varying types were frequent in the language of Alzheimers and Huntingtons Disease patients; only long-duration silent hesitations were frequent in Parkinsons language samples. Syntactic complexity was reduced in Huntingtons Disease. Verbal paraphasias were found in both the language of Alzheimers patients, as well as moderately advanced Huntingtons patients. Closed class phrases were predominant in the language of Alzheimers patients and Huntingtons patients, and open class phrases in the language of Parkinsons patients. Taken together, the results suggest that (1) there is a unique neurolinguistic profile for spontaneous language production for each neurodegenerative disease, (2) pathology of the neostriatum disrupts syntactic organization, (3) adaptive strategies are used to cope with verbal and speech-motor difficulties, and (4) adaptive strategies fail to be effective with increasing disease severity.