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Neuroimaging research with children: Ethical issues and case scenarios
Abstract
There are few available resources for learning and teaching about ethical issues in neuroimaging research with children, who constitute a special and vulnerable population. Here, a brief review of ethical issues in developmental research, situated within the emerging field of neuroethics, highlights the increasingly interdisciplinary nature of research with children. Traditional boundaries between behavioural, psychological, neuroscientific and educational research are being blurred by multidisciplinary studies of learning and human development. Developmental and educational researchers need to be aware of the ethical quandaries inherent in such research, and moral educators need to encourage researchers to consider the ethical aspects of developmental neuroimaging. To this end, fictional case scenarios were designed to address two topics in the ethical conduct of neuroimaging research with children: inadvertent findings in paediatric neuroimaging and inclusion of young children in pharmacological clinical trials. The latter is contrasted with an educational trial in an alternate scenario, underscoring similarities in ethical issues across types of developmental research. It is hoped that discussions elicited by such scenarios will contribute to both moral education and paediatric neuroethics.
... In total, 11 themes emerged during the coding process (Table 1). In 14 of the papers, the primary ethical concerns focused on the utility of research scans to diagnose and facilitate medical decision-making about IFs (4,6,8,10,14-23) and detection practices for IFs (n ¼ 14) (4,7,8,10,15,16,18,(20)(21)(22)(24)(25)(26)(27). Because research scans are not necessarily optimized for diagnosis, some researchers use clinical grade scans when children are patients enrolled in a study. ...
... The remaining concerns revolved around informed consent (n ¼ 13) (8,10,(14)(15)(16)(17)(18)(19)(20)22,24,27,28), psychological risks associated with scanning procedures and disclosure of IFs (n ¼ 13) (4,8,10,14,16,17,20,22,23,(25)(26)(27)(28), the disclosure process itself (n ¼ 12) (4,6,8,10,15,16,20,(22)(23)(24)(25)27), the economic burden of screening for and following up IFs (n ¼ 11) (4,7,8,10,14,15,17,20,21,24,28), physical risks associated with scans (n ¼ 9) (8,14,16,17,20,23,25,26,28), the burden of responsibility for the principal investigator (n ¼ 8) (4,8,10,15,18,23,24,27), uncertainties in the interpretation of results (n ¼ 8) (4,8,14,(16)(17)(18)21,26), confidentiality (n ¼ 6) (15)(16)(17)23,25,27), and therapeutic misconception (n ¼ 6) (8,10,17,18,20,25). ...
... The remaining concerns revolved around informed consent (n ¼ 13) (8,10,(14)(15)(16)(17)(18)(19)(20)22,24,27,28), psychological risks associated with scanning procedures and disclosure of IFs (n ¼ 13) (4,8,10,14,16,17,20,22,23,(25)(26)(27)(28), the disclosure process itself (n ¼ 12) (4,6,8,10,15,16,20,(22)(23)(24)(25)27), the economic burden of screening for and following up IFs (n ¼ 11) (4,7,8,10,14,15,17,20,21,24,28), physical risks associated with scans (n ¼ 9) (8,14,16,17,20,23,25,26,28), the burden of responsibility for the principal investigator (n ¼ 8) (4,8,10,15,18,23,24,27), uncertainties in the interpretation of results (n ¼ 8) (4,8,14,(16)(17)(18)21,26), confidentiality (n ¼ 6) (15)(16)(17)23,25,27), and therapeutic misconception (n ¼ 6) (8,10,17,18,20,25). ...
MRI is used routinely in research with children to generate new knowledge about brain development. The detection of unexpected brain abnormalities (incidental findings; IFs) in these studies presents unique challenges. While key issues surrounding incidence and significance, duty of care, and burden of disclosure have been addressed substantially for adults, less empirical data and normative analyses exist for minors who participate in minimal risk research. To identify ethical concerns and fill existing gaps, we conducted a comprehensive review of papers that focused explicitly on the discovery of IFs in minors. The discourse in the 21 papers retrieved for this analysis amply covered practical issues such as informed consent and screening, difficulties in ascertaining clinical significance, the economic costs and burden of responsibility on researchers, and risks (physical or psychological). However, we found little discussion about the involvement of minors in decisions about disclosure of IFs in the brain, especially for IFs of low clinical significance. In response, we propose a framework for managing IFs that integrates practical considerations with explicit appreciation of rights along the continuum of maturity. This capacity-adjusted framework emphasizes the importance of involving competent minors and respecting their right to make decisions about disclosure. J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.
... Having considered some, but certainly not all, of the practical and conceptual challenges faced by the field of Mind, Brain, and Education, the present discussion now turns to the ethical challenges that this field of inquiry has encountered as well as those that might lie in its future paths. This discussion will not consider ethical challenges associated with the use of neuroimaging methods to study the developing brain (for an excellent discussion of such challenges, see : Coch 2007). Instead the present section will consider broad ethical challenges that lie at the conceptual, rather than the methodological, level of Mind, Brain, and Education as a new field of inquiry. ...
Recent years have seen a tremendous growth in efforts to connect rapidly growing insights into how the brain learns to the field of education. Different names have been given to such efforts, including “Educational Neuroscience” and “Mind, Brain, and Education.” The aim of this chapter is to discuss these recent efforts and to provide an overview of the conceptual, practical, and ethical challenges faced by these novel, transdisciplinary efforts. To do so, the chapter begins with an overview of some examples of recent research efforts to connect research on Mind, Brain, and Education (MBE). To do so, the chapter begins with an overview of some examples of recent research in the emerging field of Mind, Brain and Education. Specifically, the chapter reviews evidence from the study of the neurocognitive processes of typical and atypical reading development in an effort to illustrate the merit of MBE. This is followed by a discussion of the conceptual and practical challenges that MBE needs to consider, such as the level at which evidence from the study of neurocognitive processes can influence education and how neuroscientists and educators can play complementary roles in the construction of the field. Against this background, the chapter considers ethical challenges, including the need to effectively and accurately communicate evidence, to carefully consider the commercialization of neuroscience, including the use of brain stimulation, to enhance cognitive functions and for classroom application.
... Differences in potential risks and benefits of educational and pharmaceutical interventions may explain how the intensity of the debate can vary, but not how two contrasting sets of attitudes have come to prevail in these two fields of enquiry. It has been pointed out that the basic ethical dilemma are similar, whether trialling methylphenidate or an educational intervention [28]. Thus, despite sharing similar underlying principles of respect for the human condition, there appear to be cultural differences between the different ethical perspectives that may be used to guide neuroeducational research, suggesting there is a need to develop an acceptable ethical framework that specifically applies to such work. ...
This paper argues that many ethical issues in neuroeducational research cannot be appropriately addressed using the principles
and guidance available in one of these areas alone, or by applying these in simple combination. Instead, interdisciplinary
and public dialogue will be required to develop appropriate normative principles. In developing this argument, it examines
neuroscientific and educational perspectives within three broad categories of ethical issue arising at the interface of cognitive
neuroscience and education: issues regarding the carrying out of interdisciplinary research, the scrutiny and communication
of findings and concepts, and the application of research and associated issues of policy likely to arise in the future. To
help highlight the need for interdisciplinary and public discussion, we also report the opinions of a group of educators (comprising
trainee teachers, teachers and head teachers) on the neuroeducational ethics of cognitive enhancing drugs, infant screening,
genetic profiling and animal research.
KeywordsEducational neuroscience–Neuroeducational research–Education–Cognitive enhancing drugs–Infant screening–Genetic profiling–Animal research
Aim
This specific review aims to expose clinicians, researchers, and administrators in hospitals to the importance, procedures, and safety of fMRI studies to promote the increased utilization of such studies in different geographical places worldwide.
The child's brain is developing rapidly, both structurally and functionally. These functional changes can only be detected using functional scans generated from an MRI machine and referred to as a functional MRI (fMRI). This method may be used clinically in complex medical and surgical conditions (e.g., epilepsy surgery), but these days is often used for research purposes. However, due to ethical and logistical considerations, fMRI in the pediatric population is not widely and equally used in different geographical places.
Conclusions
The benefits of using this method to define the functional changes occurring in the developing brain are discussed in this review, along with desensitization methods recommended when working with this vulnerable population in research and even in a clinical setting.
Background:
Neuroethics describes several interdisciplinary topics exploring the application and implications of engaging neuroscience in societal contexts. To explore this topic, we present Part 3 of a four-part bibliography of neuroethics' literature focusing on the "ethics of neuroscience."
Methods:
To complete a systematic survey of the neuroethics literature, 19 databases and 4 individual open-access journals were employed. Searches were conducted using the indexing language of the U.S. National Library of Medicine (NLM). A Python code was used to eliminate duplications in the final bibliography.
Results:
This bibliography consists of 1137 papers, 56 books, and 134 book chapters published from 2002 through 2014, covering ethical issues in neuroimaging, neurogenetics, neurobiomarkers, neuro-psychopharmacology, brain stimulation, neural stem cells, neural tissue transplants, pediatric-specific issues, dual-use, and general neuroscience research issues. These works contain explanations of recent research regarding neurotechnology, while exploring ethical issues in future discoveries and use.
This chapter provides an overview of some of the challenges and benefits to building the evolving field of mind, brain, and education (MBE). It discusses selected challenges associated with making meaningful connections across the fields of psychology, neuroscience, and education (e.g., differing levels of explanation, different methodological research, and design issues); addresses some of the mechanisms that need to be in place in order to make such connections (e.g., transdisciplinary training for educators and neuroscientists, blurring the traditional applied versus basic research distinction); and offers suggestions about the next steps to take in order to build and sustain an interdisciplinary science of MBE that provides a new, integrated, and multilevel perspective on child development, learning, and teaching. As traditional boundaries among behavioural, psychological, neuroscientific, and educational research are increasingly crossed, the chapter concludes that neuroscience should be considered one source of evidence that can contribute to evidence-based practice and policy in education, that the challenges to constructing meaningful connections between education and neuroscience are surmountable, and that the science and art of education can be connected and integrated in principled ways.
Neuroimaging practice and research are overviewed in this paper through an ethics lens. The main ethical implications in biomedical research concerning functional brain imaging are discussed with the focus on issues related to imaging of personal information and privacy. Specific norms and guidelines will be eventually formed in the future under the umbrella of the new discipline of Neuroethics.
Does the structure of an adult human brain alter in response to environmental demands? Here we use whole-brain magnetic-resonance imaging to visualize learning-induced plasticity in the brains of volunteers who have learned to juggle. We find that these individuals show a transient and selective structural change in brain areas that are associated with the processing and storage of complex visual motion. This discovery of a stimulus-dependent alteration in the brain's macroscopic structure contradicts the traditionally held view that cortical plasticity is associated with functional rather than anatomical changes.
The "In Search of . . ." television series is no way to present history, Mr. Bruer points out, and the brain-based education literature is not the way to present the science of learning.
Recent advances in the brain sciences have dramatically improved our understanding of brain function. As we find out more and more about what makes us tick, we must stop and consider the ethical implications of this new found knowledge. Will having a new biology of the brain through imaging make us less responsible for our behavior and lose our free will? Should certain brain scan studies be disallowed on the basis of moral grounds? Why is the media so interested in reporting results of brain imaging studies? What ethical lessons from the past can best inform the future of brain imaging? These compelling questions and many more are tackled by a group of contributors to this book on neuroethics. The wide range of disciplinary backgrounds that this book represents, from neuroscience, bioethics and philosophy, to law, social and health care policy, education, religion, and film, allow for profoundly insightful and provocative answers to these questions, and open up the door to a host of new ones. The contributions highlight the timeliness of modern neuroethics today, and assure the longevity and importance of neuroethics for generations to come.
This contribution explores how the emerging goals, approaches, and methodologies of design experiments might be productively combined with methods of inquiry common in more traditional laboratory science and considers the potential benefits of such a dialectic. The authors hope to promote a constructive dialogue to help formulate an infrastructure for the science of education that synthesizes theoretical insights supported by a wide array of investigational methodologies (Posner & McCandliss, 1993).
Children have been exposed to unjustifiable risks that in some cases amount to research abuse. Powerful, financially interconnected stakeholders control all facets of research, including the approval process. Physician investigators, their academic institutions, and institutional review boards (IRBs) all come under the influence of funding sponsors, whose interests conflict with the best interest of children. Children cannot rely on IRBs or on any of the existing research oversight agencies to protect them, for research too often takes inordinate risks in the name of the greater good.
Recent advances in the brain sciences have dramatically improved our understanding of brain function. As we find out more and more about what makes us tick, we must stop and consider the ethical implications of this new found knowledge. Will having a new biology of the brain through imaging make us less responsible for our behavior and lose our free will? Should certain brain scan studies be disallowed on the basis of moral grounds? Why is the media so interested in reporting results of brain imaging studies? What ethical lessons from the past can best inform the future of brain imaging? These compelling questions and many more are tackled by a group of contributors to this book on neuroethics. The wide range of disciplinary backgrounds that this book represents, from neuroscience, bioethics and philosophy, to law, social and health care policy, education, religion, and film, allow for profoundly insightful and provocative answers to these questions, and open up the door to a host of new ones. The contributions highlight the timeliness of modern neuroethics today, and assure the longevity and importance of neuroethics for generations to come.
The primary responsibility of the American Psychological Association's (APA) Committee on Standards in Research (CSR) is to advise the APA on issues and standards related to the protection of human participants in psychological research. A related goal is to enhance the use of good ethical practices by APA members. The purpose of this article is to foster the view of research ethics not as an affront to the integrity of sound research, but as opportunities for scientific rewards, including increased understanding of the meaning of data, enhanced recruitment, and the inclusion of more representative samples. Three ethical practices are discussed as examples of this general premise: respect for confidentiality, use of debriefing, and assurance that participants are noncoerced volunteers. The Committee's intent is to promote consideration of these issues, not to promulgate specific guidelines or procedures.
This study examined the quality of children's assent to a clinical trial. In subjects younger than 9 years of age, understanding of most aspects of the study was found to be poor to non-existent. Understanding of procedures was poor in almost all subjects. In addition, voluntariness may have been compromised in many subjects by their belief that failure to complete the study would displease others. If the fact that a child's assent has been obtained is used to justify the exposure of that child to the potential harm of a non-therapeutic blood sample, the assent must be meaningful. In the nutrition study observed here, the quality of the assent of children younger than 9 years of age was very poor. The assent therefore did not provide a valid justification for requesting a blood sample from these children. This study indicates that most children younger than 9 years of age cannot be expected to consent or assent to clinical research in a meaningful way. The current age of 7 years for initiating assent (in addition to parental consent) is possibly not appropriate and should be reconsidered.
Functional MRI revealed differences between children with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls in their frontal-striatal function and its modulation by methylphenidate during response inhibition. Children performed two go/no-go tasks with and without drug. ADHD children had impaired inhibitory control on both tasks. Off-drug frontal-striatal activation during response inhibition differed between ADHD and healthy children: ADHD children had greater frontal activation on one task and reduced striatal activation on the other task. Drug effects differed between ADHD and healthy children: The drug improved response inhibition in both groups on one task and only in ADHD children on the other task. The drug modulated brain activation during response inhibition on only one task: It increased frontal activation to an equal extent in both groups. In contrast, it increased striatal activation in ADHD children but reduced it in healthy children. These results suggest that ADHD is characterized by atypical frontal-striatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.
Pediatric neuroimaging studies1, 2, 3, 4, 5, up to now exclusively cross sectional, identify linear decreases in cortical gray matter and increases in white matter across ages 4 to 20. In this large-scale longitudinal pediatric neuroimaging study, we confirmed linear increases in white matter, but demonstrated nonlinear changes in cortical gray matter, with a preadolescent increase followed by a postadolescent decrease. These changes in cortical gray matter were regionally specific, with developmental curves for the frontal and parietal lobe peaking at about age 12 and for the temporal lobe at about age 16, whereas cortical gray matter continued to increase in the occipital lobe through age 20.
The study by Zito and colleagues1 in
this issue of THE JOURNAL on the use of psychotropic medications in very young
children in 2 Medicaid programs and a managed care organization suggests that
1% to 1.5% of all children 2 to 4 years old enrolled in these programs currently
are receiving stimulants, antidepressants, or antipsychotic medications. The
authors also report that the prevalence of neuropsychopharmacologic interventions
in this age group increased substantially during the last decade.
Recent reports on the use of psychotropic medications for preschool-aged children with behavioral and emotional disorders warrant further examination of trends in the type and extent of drug therapy and sociodemographic correlates.
To determine the prevalence of psychotropic medication use in preschool-aged youths and to show utilization trends across a 5-year span.
Ambulatory care prescription records from 2 state Medicaid programs and a salaried group-model health maintenance organization (HMO) were used to perform a population-based analysis of three 1-year cross-sectional data sets (for the years 1991, 1993, and 1995).
From 1991 to 1995, the number of enrollees aged 2 through 4 years in a Midwestern state Medicaid (MWM) program ranged from 146,369 to 158,060; in a mid-Atlantic state Medicaid (MAM) program, from 34,842 to 54,237; and in an HMO setting in the Northwest, from 19,107 to 19,322.
Total, age-specific, and gender-specific utilization prevalences per 1000 enrollees for 3 major psychotropic drug classes (stimulants, antidepressants, and neuroleptics) and 2 leading psychotherapeutic medications (methylphenidate and clonidine); rates of increased use of these drugs from 1991 to 1995, compared across the 3 sites.
The 1995 rank order of total prevalence in preschoolers (per 1000) in the MWM program was: stimulants (12.3), 90% of which represents methylphenidate (11.1); antidepressants (3.2); clonidine (2.3); and neuroleptics (0.9). A similar rank order was observed for the MAM program, while the HMO had nearly 3 times more clonidine than antidepressant use (1.9 vs 0.7). Sizable increases in prevalence were noted between 1991 and 1995 across the 3 sites for clonidine, stimulants, and antidepressants, while neuroleptic use increased only slightly. Methylphenidate prevalence in 2- through 4-year-olds increased at each site: MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold. Decreases occurred in the relative proportions of previously dominant psychotherapeutic agents in the stimulant and antidepressant classes, while increases occurred for newer, less established agents.
In all 3 data sources, psychotropic medications prescribed for preschoolers increased dramatically between 1991 and 1995. The predominance of medications with off-label (unlabeled) indications calls for prospective community-based, multidimensional outcome studies.
A complex problem exists about how to promote the best interests of children as a group through research while protecting the rights and welfare of individual research subjects. The Nuremberg Code forbids studies without consent, eliminating most children as subjects, and the Declaration of Helsinki disallows non-therapeutic research on non-consenting subjects. Both codes are unreasonably restrictive. Another approach is represented by the Council for the International Organizations of Medical Science, the U.S. Federal Research Guidelines, and many other national policies. They allow research ethics committees or institutional review boards to authorize studies with acceptable balances of likely benefits and harms, but neither clarify how to balance them nor explain the meaning of pivotal concepts, like "minimal risk." Paths to the improvement of balancing or consequentialist approaches include (1) improving standardizing of risk assessment, (2) rejecting crude utilitarianism, (3) identifying and justifying normative or moral judgments, and (4) acknowledging extra-regulatory thresholds and deontological or non-negotiable duties to children.
Emerging neurotechnologies, including psychopharmaceuticals, brain stimulation, implantable brain chips, transcranial magnetic stimulation, and brain imaging raise a number of ethical questions. One of the most contentious is the proper role of these technologies in improving or increasing mental and neurological traits and skills in those with no identifiable pathology. The "enhancement" debate centers around a number of concerns and philosophical approaches to the proper role of medicine, therapeutics, and desirable human qualities. Arguements for and against neurological enhancement are reviewed, and historical and social perspectives are offered.
Developmental dyslexia, characterized by unexplained difficulty in reading, is associated with behavioral deficits in phonological processing. Functional neuroimaging studies have shown a deficit in the neural mechanisms underlying phonological processing in children and adults with dyslexia. The present study examined whether behavioral remediation ameliorates these dysfunctional neural mechanisms in children with dyslexia. Functional MRI was performed on 20 children with dyslexia (8-12 years old) during phonological processing before and after a remediation program focused on auditory processing and oral language training. Behaviorally, training improved oral language and reading performance. Physiologically, children with dyslexia showed increased activity in multiple brain areas. Increases occurred in left temporo-parietal cortex and left inferior frontal gyrus, bringing brain activation in these regions closer to that seen in normal-reading children. Increased activity was observed also in right-hemisphere frontal and temporal regions and in the anterior cingulate gyrus. Children with dyslexia showed a correlation between the magnitude of increased activation in left temporo-parietal cortex and improvement in oral language ability. These results suggest that a partial remediation of language-processing deficits, resulting in improved reading, ameliorates disrupted function in brain regions associated with phonological processing and produces additional compensatory activation in other brain regions.
Context Recent reports on the use of psychotropic medications for preschool-aged
children with behavioral and emotional disorders warrant further examination
of trends in the type and extent of drug therapy and sociodemographic correlates.
Objectives To determine the prevalence of psychotropic medication use in preschool-aged
youths and to show utilization trends across a 5-year span.
Design Ambulatory care prescription records from 2 state Medicaid programs
and a salaried group-model health maintenance organization (HMO) were used
to perform a population-based analysis of three 1-year cross-sectional data
sets (for the years 1991, 1993, and 1995).
Setting and Participants From 1991 to 1995, the number of enrollees aged 2 through 4 years in
a Midwestern state Medicaid (MWM) program ranged from 146,369 to 158,060;
in a mid-Atlantic state Medicaid (MAM) program, from 34,842 to 54,237; and
in an HMO setting in the Northwest, from 19,107 to 19,322.
Main Outcome Measures Total, age-specific, and gender-specific utilization prevalences per
1000 enrollees for 3 major psychotropic drug classes (stimulants, antidepressants,
and neuroleptics) and 2 leading psychotherapeutic medications (methylphenidate
and clonidine); rates of increased use of these drugs from 1991 to 1995, compared
across the 3 sites.
Results The 1995 rank order of total prevalence in preschoolers (per 1000) in
the MWM program was: stimulants (12.3), 90% of which represents methylphenidate
(11.1); antidepressants (3.2); clonidine (2.3); and neuroleptics (0.9). A
similar rank order was observed for the MAM program, while the HMO had nearly
3 times more clonidine than antidepressant use (1.9 vs 0.7). Sizable increases
in prevalence were noted between 1991 and 1995 across the 3 sites for clonidine,
stimulants, and antidepressants, while neuroleptic use increased only slightly.
Methylphenidate prevalence in 2 through 4-year-olds increased at each site:
MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold. Decreases occurred in the relative
proportions of previously dominant psychotherapeutic agents in the stimulant
and antidepressant classes, while increases occurred for newer, less established
agents.
Conclusions In all 3 data sources, psychotropic medications prescribed for preschoolers
increased dramatically between 1991 and 1995. The predominance of medications
with off-label (unlabeled) indications calls for prospective community-based,
multidimensional outcome studies.
Edited by Judy Illes. Published by Oxford University Press, Oxford, 2006, £29.95 (softcover), pp 320. ISBN 0-19-856721-9
No-one interested in the neurosciences could fail to be stimulated by this book. It has a tremendous reach, but perhaps it oversteps the mark. For instance, there is the suggestion that neuroscience, via neuroethics, might help to solve the problem of socioeconomic disadvantage and sort out …
Context Previous reports have discussed incidental disease found on brain magnetic
resonance imaging (MRI) scans that had been requested for an unrelated clinical
concern or symptom, resulting in a selection bias for disease. However, the
prevalence of unexpected abnormalities has not been studied in a healthy population.Objective To evaluate the prevalence of incidental findings on brain MRI scans
obtained for a healthy, asymptomatic population without selection bias.Design, Setting, and Participants Retrospective analysis of brain MRI scans obtained between May 17, 1996,
and July 25, 1997, from 1000 volunteers who participated as control subjects
for various research protocols at the National Institutes of Health. All participants
(age range, 3-83 years; 54.6% male) were determined to be healthy and asymptomatic
by physician examination and participant history.Main Outcome Measure Prevalence of abnormalities on brain MRI by category of finding (no
referral necessary, routine referral, urgent referral [within 1 week of study],
and immediate referral [within 1 to several days of study]).Results Eighty-two percent of the MRI results were normal. Of the 18% demonstrating
incidental abnormal findings, 15.1% required no referral; 1.8%, routine referral;
1.1%, urgent referral; and 0%, immediate referral. In subjects grouped for
urgent referral, 2 confirmed primary brain tumors (and a possible but unconfirmed
third) were found, demonstrating a prevalence of at least 0.2%.Conclusion Asymptomatic subjects present with a variety of abnormalities, providing
valuable information on disease prevalence in a presumed healthy population.
A small percentage of these findings require urgent medical attention and/or
additional studies.
Neuroscience is a relatively new discipline encompassing neurology, psychology and biology. It has made great strides in the last 100 years, during which many aspects of the physiology, biochemistry, pharmacology and structure of the vertebrate brain have been understood. Understanding of some of the basic perceptual, cognitive, attentional, emotional and mnemonic functions is also making progress, particularly since the advent of the cognitive neurosciences, which focus specifically on understanding higher level processes of cognition via imaging technology. Neuroimaging has enabled scientists to study the human brain at work in vivo, deepening our understanding of the very complex processes underpinning speech and language, thinking and reasoning, reading and mathematics. It seems timely, therefore, to consider how we might implement our increased understanding of brain development and brain function to explore educational questions.
This book, by two psychiatrists who themselves have attention deficit disorder (ADD), provides general information and case examples on this disorder. The nine chapters cover the following topics: (1) the nature of ADD; (2) characteristics and educational experiences of the child with ADD; (3) characteristics and behavior patterns of the adult with ADD; (4) effects of ADD on couples; (5) effects of ADD on the family; (6) subtypes of ADD; (7) the diagnostic process; (8) treatment of ADD; and (9) the biology of ADD. An appendix lists resources including national organizations, state advocacy groups, suggested readings on ADD in adults, and support groups (by state). (DB)
Expresses the importance of scientifically based research in education reform and explains how to judge the validity of educational research. Describes control groups, randomized and matched experiments, statistical educational significance, sample size, and the difference between scientifically based and rigorously evaluated research. (Contains 11 references.) (WFA)
summarizes the results of EEG coherence analyses from 436 children and adolescents ranging in mean age from 6 mo to 16 yrs, with the goal of furthering our understanding of the neurophysiological dynamics of human cognitive development
[argues] that analysis of the development of EEG coherence provides fundamental information about the organization of differentiation and integration of intracortical connections during postnatal development / [postulates] that there are iterative "growth spurts" of cortical connections nested within 4-yr anatomical cycles that are marked by phase transitions
in the left hemisphere, the cycles are composed of a developmental sequence governed by anterior–posterior and lateral–medial gradients involving a sequential lengthening of intracortical connections between posterior sensory areas and frontal regions / in contrast, the cycles in the right hemisphere involve a sequential contraction of long-distance frontal connections to shorter-distance posterior sensory connections / [argues] that the left-hemisphere expanding sequence reflects a process of functional integration of differentiated subsystems, whereas the right-hemisphere contracting sequence is a process of functional differentiation of previously integrated subsystems / these left- and right-hemisphere cycles are repeated throughout the life span and are postulated to represent a process that iteratively narrows the gap between structure and function by slowly sculpting and refining the microanatomy of the brain (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Functional magnetic resonance imaging (fMRI) has quickly become the preferred technique for imaging normal brain activity, especially in the typically developing child. This technique takes advantage of specific magnetic properties and physiological processes to generate images of brain activity. These images can be interpreted as a function of group or individual based differences to explore developmental patterns and/or cognitive abilities. In this paper we present an overview of the basic principles of fMRI and a discussion of what is currently known about the physiological bases of the resulting signal. We also report findings from developmental fMRI studies that examine the development of cognitive and neural systems underlying attention and memory. Behavioral performance and age-related neural changes are examined independently in an attempt to disentangle developmental differences from individual variability in performance.
At the dawn of the 21st century, educational research is finally entering the 20th century. The use of randomized experiments that transformed medicine, agriculture, and technology in the 20th century is now beginning to affect educational policy. This article discusses the promise and pitfalls of randomized and rigorously matched experiments as a basis for policy and practice in education. It concludes that a focus on rigorous experiments evaluating replicable programs and practices is essential to build confidence in educational research among policymakers and educators. However, new funding is needed for such experiments and there is still a need for correlational, descriptive, and other disciplined inquiry in education. Our children deserve the best educational programs, based on the most rigorous evidence we can provide.
This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents.
Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors.
Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, "piggybacking" onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; "coercive" inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity.
The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects.
We interviewed 64 parents by questionnaire after completion of a clinical trial involving their children for their perceptions and attitudes about informed consent. The results show that only a small minority realized that drug trials are designed to assess not only efficacy but safety as well. More worrisome was the majority of parents who felt that drug trials conducted by hospitals are of no or low risks. Moreover, a significant minority offered the view that the strict informed consent procedures we followed were unnecessary because they would do what the doctor advised. Even more worrisome was the small percentage of parents who realized that a signed consent form was primarily meant to protect their rights, and only one-third of the parents knew of their right to withdraw their child unconditionally from the trial at any time. These findings suggest that there may be significant attitudinal barriers to parental understanding of the informed consent process.
Studies with positron emission tomography indicate that the human brain undergoes a period of postnatal maturation that is much more protracted than previously suspected. In the newborn, the highest degree of glucose metabolism (representative of functional activity) is in primary sensory and motor cortex, cingulate cortex, thalamus, brain stem, cerebellar vermis, and hippocampal region. At 2 to 3 months of age, glucose utilization increases in the parietal, temporal, and primary visual cortex; basal ganglia; and cerebellar hemispheres. Between 6 and 12 months, glucose utilization increases in frontal cortex. These metabolic changes correspond to the emergence of various behaviors during the first year of life. The measurement of absolute rates of glucose utilization during development indicates that the cerebral cortex undergoes a dynamic course of metabolic maturation that persists until ages 16-18 years. Initially, there is a rise in the rates of glucose utilization from birth until about age 4 years, at which time the child's cerebral cortex uses over twice as much glucose as that of adults. From age 4 to 10 years, these very high rates of glucose consumption are maintained, and only after then is there a gradual decline of glucose metabolic rates to reach adult values by age 16-18 years. Correlations between glucose utilization rates and synaptogenesis are discussed, and the argument is made that these findings have important implications with respect to human brain plasticity following injury as well as to "critical periods" of maximal learning capacity.
"Unidentified bright objects" (UBOs) have been observed as areas of increased T2-weighted signal intensity on MRI in 43% to 93% of children with neurofibromatosis 1 (NF1). Because of this high frequency and the fact that the NIH diagnostic criteria often do not permit diagnosis of NF1 in early childhood, UBOs have been proposed as an additional diagnostic criterion.
The authors examined the sensitivity and specificity of UBOs for NF1 in 19 affected children and 19 age-matched controls. Eleven of the control patients had CNS pathology that might be classified as UBOs on MRI scan. The authors measured the agreement in recognition of UBOs between two pediatric neuroradiologists who independently examined the MRI studies of these patients. They also assessed the effect of adding UBOs to the NIH diagnostic criteria on ability to diagnose NF1 in young patients.
Sensitivity and specificity of UBOs for NF1 averaged 97% and 79%, respectively. Agreement between the two radiologists was 84% overall, but varied greatly from one brain region to another. Adding UBOs as a diagnostic criterion permitted the diagnosis of 30% of young patients with NF1 mutations who do not meet the existing NIH diagnostic criteria for NF1. The value of including UBOs is less in older patients because a larger proportion of them meet the existing diagnostic criteria.
UBOs are difficult to identify with certainty and occur in children with suspected CNS disorders who do not have NF1, but they tend to occur in different brain regions. UBOs may be more useful for diagnosis of NF1 in young children if they can be defined precisely and if only the cerebellum, brainstem, and basal ganglia are considered.
Despite significant gains in the fields of pediatric neuroimaging and developmental neurobiology, surprisingly little is known about the developing human brain or the neural bases of cognitive development. This paper addresses MRI studies of structural and functional changes in the developing human brain and their relation to changes in cognitive processes over the first few decades of human life. Based on post-mortem and pediatric neuroimaging studies published to date, the prefrontal cortex appears to be one of the last brain regions to mature. Given the prolonged physiological development and organization of the prefrontal cortex during childhood, tasks believed to involve this region are ideal for investigating the neural bases of cognitive development. A number of normative pediatric fMRI studies examining prefrontal cortical activity in children during memory and attention tasks are reported. These studies, while largely limited to the domain of prefrontal functioning and its development, lend support for continued development of attention and memory both behaviorally and physiologically throughout childhood and adolescence. Specifically, the magnitude of activity observed in these studies was greater and more diffuse in children relative to adults. These findings are consistent with the view that increasing cognitive capacity during childhood may coincide with a gradual loss rather than formation of new synapses and presumably a strengthening of remaining synaptic connections. It is clear that innovative methods like fMRI together with MRI-based morphometry and nonhuman primate studies will transform our current understanding of human brain development and its relation to behavioral development.
The obligation of society to improve the welfare of its members requires the conduct of paediatric drug trials. Nevertheless, research activities must satisfy obligations to individual participants.
The obligation to protect the welfare of children requires that nontherapeutic research procedures generally involve no more than minimal risk. It also requires that randomisation occurs only when the relative merits of therapeutic procedures remain unsettled among the relevant community of experts.
The duty to respect the developing autonomy of children requires that they be included in decision-making about research participation in a manner consistent with the level of their decision-making capacity. However, when children lack mature decision-making capacities, the duty of parents to protect their welfare may properly constrain their choices.
Justice requires that the benefits and burdens of research be distributed in a manner that assures equal opportunity for all children. Vulnerable children should receive special protection against the burdens of nontherapeutic research procedures. The benefits of participating in clinical trials should be available to all children with serious illnesses for which current treatment is unsatisfactory. Justice also requires that initiatives be undertaken to rectify current shortcomings in the scope of paediatric drug research.
Striking an appropriate balance between obligations to conduct research and to protect the interests of participants is essential to the moral integrity of paediatric drug research.
In response to concerns about the increasing use of psychotropic medications in preschoolers, the National Institute of Mental Health and the Food and Drug Administration convened a workshop in October 2000 to examine the current state of knowledge regarding psychopharmacology for young children and discuss a variety of topics relevant to research in this age group, including safety, efficacy, investigational methods, and ethical aspects. The meeting gathered researchers, practitioners, ethicists, industry staff, and family and patient representatives. Efficacy and safety of psychotropics have not been systematically evaluated in preschoolers. The major limitation to this research is the diagnostic uncertainty surrounding most manifestations of psychopathology in early childhood. Research in developmental psychopathology is needed to clarify diagnosis and provide sensitive and specific methods for clinical trials. Possible approaches to expanding the research basis of this area of clinical practice, including a recently started study of methylphenidate in preschoolers, are reported here.
As with all newborns, picking a name is a difficult and contentious task. One of the most animated debates at the close of the NMTF conference was about the appropriateness of the label “Neuroethics.” Some claimed it was an unfortunate name for this fledgling field, because ethics is the purview of philosophers, while the field clearly needs the concerted interaction of policy makers, lawyers, journalists, and the public, as well as the philosophers and neuroscientists. Others suggested that “Neuroethics” was ill-chosen because ethics excluded nonethicist philosophers and other humanists. I disagree on both counts. “Neuroethics” is a name well-chosen for a number of reasons. First, it is concise, catchy, and evocative. Second, it is a sad misconception of all too many that ethics is merely an academic exercise of philosophers. Rather, our ability to think and act ethically is arguably one of the defining things of what it is to be human: it is an inclusive rather than an exclusive term. Part of what it is to be a scientist, a doctor, a lawyer, a politician, or a journalist is to execute one's office in accordance with the values of one's profession and the society at large. Witness the Hippocratic oath, the courtroom oath, the swearing in before taking office, and the injunction not to fabricate stories or data. Ethics should therefore not be a domain foreign to nonethicist professionals. Moreover, in the time of Plato and Aristotle, it was considered imperative for every citizen to have a moral education and to take part in the ethical deliberations of society. It is perhaps reflective of some of the ills in our society that ethics is thought to be a philosopher's concern and not the common man's. But this is not a misconception we should yield to—it is an invitation to reeducate the public that ethics is a forum that needs the participation of everyone. Rather than capitulate to a narrow view of what ethics is and who it concerns, we should embrace the dialectical model of the NMTF meeting and demonstrate that ethics is as broad and inclusive a category as any.We should not merely pay lip-service to this inclusiveness. Neuroethics has the potential to be an interdisciplinary field with wide-ranging effects. However, because it ultimately impinges on the well-being of the individual and our society, it is not a study that can or should be undertaken in the ivory tower. It is imperative that neuroethicists take part in a dialogue with the public. To make this possible, however, it is important in the short term to strive for “neuroliteracy” of the public and the media. We must make a concerted effort to make the subtleties of neuroscientific research accessible to the lay public via the media and refrain from the current practice of feeding it sound bites. For it is only with a nuanced understanding of the science, and a renewed trust in the goals of neuroscientists, that real progress will be made on these difficult issues. In the last few months, we have heard just the first noises of such a dialogue. As Dana Foundation executive director Francis Harper aptly noted at the close of NMTF, “You can call it what you want, but the neuroethics train has left the station.”
There is growing public awareness of the ethical issues raised by progress in many areas of neuroscience. This commentary reviews the issues, which are triaged in terms of their novelty and their imminence, with an exploration of the relevant ethical principles in each case.
Previous studies have addressed the prevalence of incidental findings in symptomatic and healthy adult populations. Our study aims to elucidate the prevalence of incidental findings in a healthy pediatric population.
We retrospectively reviewed 225 conventional brain MR imaging studies obtained during structural and functional brain imaging research in a cohort of neurologically healthy children (100 boys [44%] and 125 girls [56%]) ranging in age from younger than 1 month to 18 years. All MR images were reviewed, and two board-certified neuroradiologists categorized the findings by consensus.
Incidental abnormalities were detected in 47 subjects (21%), while 79% of the images were normal. Of the 47 abnormalities detected, 17 (36%) required routine clinical referral; a single lesion (2%) required urgent referral. The occurrence of these findings in the male cohort was twice that of the female cohort; however, the percentage of subjects requiring either routine or urgent referral did not differ by sex (male subjects, 34%; female subjects, 39%).
Although the frequency of clinically important incidental abnormalities was not high in the sample of children studied, the presence and variety of findings in any pediatric group is particularly important for both the welfare of the subject and for research in which knowledge of the subject's neurologic status is vital to the interpretation of the results. Despite the limitations of the study in terms of the age and ethnic distribution, this work highlights the need for the routine involvement of trained radiologists in these studies to ensure that such incidental findings are detected and that appropriate follow-up is provided.
Neuroimaging in pediatrics is accompanied by all the ethical dilemmas associated with neuroimaging in adults, magnified significantly. The defining characteristics of childhood make working ethically with the population particularly problematic. Children have not developed the rational capabilities necessary to make informed decisions and the variability and change associated with development contribute to heightened risks and/or benefits of any procedure and limit interpretation of data. As a consequence, fewer pediatric than adult neuroimaging research studies have been done, further limiting general knowledge of the field. Significant strides have been made just within the past few years with the collection of normative data sets of healthy children. Recommendations on how to proceed with pediatric neuroimaging studies while ensuring ethical treatment of the participants are presented.
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.
Increased community utilization of psychotropic medications among children has brought attention to pediatric psychopharmacology research and associated ethical issues.
To discuss ethical aspects of child participation in psychopharmacology protocols.
Selective review of relevant scientific and regulatory literature.
Efficacy and safety of psychotropics in children cannot be entirely inferred from adult data and direct participation of children in research is necessary. Child research must follow special regulations that are in addition to those common to all human research. For research with prospect of direct benefit, a critical factor is whether the risk/benefit ratio is favorable to the participating child. For research without such a prospect, the concepts of minimal risk and minor increase over minimal risk apply. However, the interpretation and application of these principles to specific protocols vary across settings and among ethics committees. Thus far, little empirical investigation has been conducted on children and parents' motivation for research participation, effectiveness of the informed consent and assent procedures, possibility of persistent consequences of exposure to experimental treatments and placebo, and validation of the concepts of minimal risk and minor increase over minimal risk.
Research on human subject issues relevant to child participation is a promising approach to improving ethical methods and procedures of pediatric psychopharmacology.
Since children are considered incapable of giving informed consent to participate in research, regulations require that both parental permission and the assent of the potential child subject be obtained. Assent and permission are uniquely bound together, each serving a different purpose. Parental permission protects the child from assuming unreasonable risks. Assent demonstrates respect for the child and his developing autonomy. In order to give meaningful assent, the child must understand that procedures will be performed, voluntarily choose to undergo the procedures, and communicate this choice. Understanding the elements of informed consent has been the paradigm for assessing capacity to give assent. This method leaves the youngest, least cognitively mature children vulnerable to waiver of assent and forced research participation. Voluntariness can also be compromised by the influence of authority figures who can exert undue influence and coerce children to participate in research. This paper discusses factors that may influence the decision to give assent/permission, potential parent-child conflict in the assent/permission process and how it is resolved, and potential parental undue influence on research participation. These issues are illustrated with quotations drawn from a larger qualitative study of parental permission and child assent (data not presented). We suggest a developmental approach, viewing assent as a continuum ranging from mere affirmation in the youngest children to the equivalent of the informed consent process in the mature adolescent.
When children are too young to make their own autonomous decisions, decisions have to be made for them. In certain contexts we allow parents and others to make these decisions, and do not interfere unless the decision clearly violates the best interest of the child. In other contexts we put a priori limits on what kind of decisions parents can make, and/or what kinds of considerations they have to take into account. Consent to medical research currently falls into the second group mentioned here. We want to consider and ultimately reject one of the arguments put forward for putting medical research into the second category. We will argue that some objections to children's participation in research are either based on an implausibly restrictive conception of what is in fact in the child's best interests or that there is an implicit and false premise hidden in this argument; i.e., the premise that our children have so deeply fallen into moral turpitude that we must assume that they would not want to fulfill their moral obligations, or, that they will grow up to be morally deficient and will then wish not to have acted well while a child.