Why mental disorders are brain disorders. And why they are not: ADHD and the challenges of heterogeneity and reification.

Scientific attempts to identify biomarkers to reliably diagnose mental disorders have thus far been unsuccessful. This has inspired the Research Domain Criteria (RDoC) approach which decomposes mental disorders into behavioral, emotional, and cognitive domains. This perspective article argues that the search for biomarkers in psychiatry presupposes that the present mental health categories reflect certain (neuro-) biological features, that is, that these categories are reified as biological states or processes. I present two arguments to show that this assumption is very unlikely: First, the heterogeneity (both within and between subjects) of mental disorders is grossly underestimated, which is particularly salient for an example like Attention Deficit/Hyperactivity Disorder (ADHD). Second, even the search for the biological basis of psychologically more basic categories (cognitive and emotional processes) than the symptom descriptions commonly used in mental disorder classifications has thus far been inconclusive. While philosophers have discussed this as the problem of mind-body-reductionism for ages, Turkheimer presented a theoretical framework comparing weak and strong biologism which is more useful for empirical research. This perspective article concludes that mental disorders are brain disorders in the sense of weak, but not strong biologism. This has important implications for psychiatric research: The search for reliable biomarkers for mental disorder categories we know is unlikely to ever be successful. This implies that biology is not the suitable taxonomic basis for psychiatry, but also psychology at large.

Stable Consciousness? The "Hard Problem" Historically Reconstructed and in Perspective of Neurophenomenological Research on Meditation.

Finding a scientific, third-person explanation of subjective experience or phenomenal content is commonly called the "hard problem" of consciousness. There has recently been a surge in neuropsychological research on meditation in general and long-term meditators in particular. These experimental subjects are allegedly capable of generating a stable state of consciousness over a prolonged period of time, which makes experimentation with them an interesting paradigm for consciousness research. This perspective article starts out with a historical reconstruction of the "hard problem," tracing it back to Gottfried Wilhelm Leibniz and Emil du Bois-Reymond in the 18th and 19th century, respectively, and the problem of introspection as already acknowledged by Wilhelm Wundt in the 19th century. It then discusses the prospects of research on long-term meditators from a contemporary perspective and with respect to the neurophenomenological research program already advocated by Francisco J. Varela.

Neuroscience Education Begins With Good Science: Communication About Phineas Gage (1823-1860), One of Neurology's Most-Famous Patients, in Scientific Articles.

Phineas Gage is one of the most famous neurological patients. His case is still described in psychology textbooks and in scientific journal articles. A controversy has been going on about the possible consequences of his accident, destroying part of his prefrontal cortex, particularly with respect to behavioral and personality changes. Earlier studies investigated the accuracy of descriptions in psychology textbooks. This is, to my knowledge, the first analysis of journal articles in this respect. These were investigated with regard to four criteria: Description of (1) personality changes, (2) psychopathy-like behavior, (3) alternative explanations besides the immediate brain damage, and (4) Gage's recovery. 92% of articles described personality changes, 52% of a psychopathy-like kind; only 4% mentioned alternative explanations and 16% described Gage's recovery. The results are discussed in the light of the available historical evidence. The article closes with several suggestions on improving science communication about the famous case.

Neurorights in History: A Contemporary Review of José M. R. Delgado's "Physical Control of the Mind" (1969) and Elliot S. Valenstein's "Brain Control" (1973).

Scholars from various disciplines discuss the ethical, legal, and social implications of neurotechnology. Some have proposed four concrete "neurorights". This review presents the research of two pioneers in brain stimulation from the 1950s to 1970s, José M. R. Delgado and Elliot S. Valenstein, who also reflected upon the ethical, legal, and social aspects of their and other scientists' related research. Delgado even formulated the vision "toward a psychocivilized society" where brain stimulation is used to control, in particular, citizens' aggressive and violent behavior. Valenstein, by contrast, believed that the brain is not organized in such a way to allow the control or even removal of only negative processes without at the same time diminishing desirable ones. The paper also describes how animal and human experimentation on brain stimulation was carried out in that time period. It concludes with a contemporary perspective on the relevance of neurotechnology for neuroethics, neurolaw, and neurorights, including two recent examples for brain-computer interfaces.

Neuroenhancement as Instrumental Drug Use: Putting the Debate in a Different Frame.

The use of performance-enhancing drugs to study or work better is often called "cognitive enhancement" or "neuroenhancement" and sparked a debate between scholars from many disciplines. I argue that such behavior can better be subsumed under the more general category of "instrumental drug use". This broader perspective allows understanding neuroenhancement better from the perspective of addiction medicine and public health and supports a more consistent drug policy. I also summarize the most important systematic reviews and individual surveys of nonmedical substance use to study or work better. Different definitions and methodologies limit the comparability of these studies. The unified approach of drug instrumentalization would partially solve such problems. Finally, prevalence studies from the 1960s to 1980s as well as anecdotal evidence since the late 19th century show that instrumental drug use is and has been for a long time a common phenomenon. It should thus also be investigated and treated accordingly.

Real Neurolaw in the Netherlands: The Role of the Developing Brain in the New Adolescent Criminal Law.

Previous publications discussed the conditions under which courts admitted or could admit neurotechnological evidence like brain scans. There were also first attempts to investigate legal decisions neuroscientifically. The present paper analyzes a different way in which neuroscience already influenced the law: The legal justification of the new Dutch adolescent criminal law explicitly mentions findings on brain development to justify a higher maximum age for the application of juvenile criminal law than before. The lawmaker's reasoning is compared with the neuroscientific studies on which it is based. In particular, three neurodevelopmental publications quoted by the Dutch Council for the Administration of Criminal Justice and Protection of Juveniles to justify that adolescents can be legally less responsible are analyzed in detail. The paper also addresses possibilities under which brain research could improve legal decision-making in the future. One important aspect turns out to be that neuroscience should not only matter on the level of justification, but also provide better instruments on the individual level of application.

Subjective Experience, Heterophenomenology, or Neuroimaging? A Perspective on the Meaning and Application of Mental Disorder Terms, in Particular Major Depressive Disorder.

Increasing research efforts try to identify biological markers in order to support or eventually replace current practices of diagnosing mental disorders. Inasmuch as these disorders refer to subjective mental states, such efforts amount to their objectification. This gives rise to conceptual as well as empirical challenges: What kind of things are mental disorders? And how to deal with situations where subjective reports, clinical decisions, and brain scans contradict each other? The present paper starts out with a discussion of recent efforts to objectify beauty. Such attempts to quantify and localize psychological constructs in the brain are compared to earlier examples from the history of psychology. The paper then discusses personal and social implications of the objectification of subjective mental states, including mental disorders. The construct of Major Depressive Disorder, one of the most prevalent mental disorders, is then analyzed in more detail. It turns out that this is a very complex construct probably associated with highly heterogeneous actual instances of the disorder. It is then shown that it is unlikely to replace these symptoms' descriptions with patterns of brain activations, at least in the near future, given these patterns' empirical lack of specificity. The paper then discusses which of the disorder's core symptoms are more or less amenable to behavioral or neuroscientific investigation and analyses whether the heterophenomenological method can solve the problem. The conclusion is that the disorder construct is neither entirely subjective, nor completely objectifiable, and that clinical experts do well by continuing to take a pragmatical stance.

How Realistic Are the Scientific Assumptions of the Neuroenhancement Debate? Assessing the Pharmacological Optimism and Neuroenhancement Prevalence Hypotheses.

Since two decades, neuroenhancement is a major topic in neuroethics and still receives much attention in the scholarly literature as well as in public media. In contrast to high hopes at the beginning of the "Decade of the Brain" in the United States and Europe that we subsume under the "pharmacological optimism hypothesis," recent evidence from clinical neuroscience suggests that developing drugs that make healthy people smarter is even more difficult than finding new treatments for patients with mental disorders. However, cognitive enhancing drugs even for patients with impaired intellectual performance have not been successfully developed yet and new drugs that might have a disruptive impact on this field are unlikely to be developed in the near future. Additionally, we discuss theoretical, empirical, and historical evidence to assess whether cognitive enhancement of the healthy is common or even epidemic and if its application will further increase in the near future, as suggested by the "neuroenhancement prevalence hypothesis." Reports, surveys, and reviews from the 1930s until today indicate that psychopharmacological neuroenhancement is a fact but less common than often stated, particularly in the public media. Non-medical use of psychostimulants for the purpose of cognitive enhancement exists since at least 80 years and it might actually have been more common in the past than today. Therefore, we conclude that the pharmacological optimism hypothesis and neuroenhancement prevalence hypotheses have to be rejected and argue that the neuroenhancement debate should take the available evidence more into account.

Methodological Problems on the Way to Integrative Human Neuroscience.

Neuroscience is a multidisciplinary effort to understand the structures and functions of the brain and brain-mind relations. This effort results in an increasing amount of data, generated by sophisticated technologies. However, these data enhance our descriptive knowledge, rather than improve our understanding of brain functions. This is caused by methodological gaps both within and between subdisciplines constituting neuroscience, and the atomistic approach that limits the study of macro- and mesoscopic issues. Whole-brain measurement technologies do not resolve these issues, but rather aggravate them by the complexity problem. The present article is devoted to methodological and epistemic problems that obstruct the development of human neuroscience. We neither discuss ontological questions (e.g., the nature of the mind) nor review data, except when it is necessary to demonstrate a methodological issue. As regards intradisciplinary methodological problems, we concentrate on those within neurobiology (e.g., the gap between electrical and chemical approaches to neurophysiological processes) and psychology (missing theoretical concepts). As regards interdisciplinary problems, we suggest that core disciplines of neuroscience can be integrated using systemic concepts that also entail human-environment relations. We emphasize the necessity of a meta-discussion that should entail a closer cooperation with philosophy as a discipline of systematic reflection. The atomistic reduction should be complemented by the explicit consideration of the embodiedness of the brain and the embeddedness of humans. The discussion is aimed at the development of an explicit methodology of integrative human neuroscience, which will not only link different fields and levels, but also help in understanding clinical phenomena.

Critical neuroscience-or critical science? A perspective on the perceived normative significance of neuroscience.

Members of the Critical Neuroscience initiative raised the question whether the perceived normative significance of neuroscience is justified by the discipline's actual possibilities. In this paper I show how brain research was assigned the ultimate political, social, and moral authority by some leading researchers who suggested that neuroscientists should change their research priorities, promising solutions to social challenges in order to increase research funds. Discussing the two examples of cognitive enhancement and the neuroscience of (im)moral behavior I argue that there is indeed a gap between promises and expectations on the one hand and knowledge and applications on the other. However it would be premature to generalize this to the neurosciences at large, whose knowledge-producing, innovative, and economic potentials have just recently been confirmed by political and scientific decision-makers with the financial support for the Human Brain Project and the BRAIN Initiative. Finally, I discuss two explanations for the analyzed communication patterns and argue why Critical Neuroscience is necessary, but not sufficient. A more general Critical Science movement is required to improve the scientific incentive system.

Brains in context in the neurolaw debate: the examples of free will and "dangerous" brains.

Will neuroscience revolutionize forensic practice and our legal institutions? In the debate about the legal implications of brain research, free will and the neural bases of antisocial or criminal behavior are of central importance. By analyzing frequently quoted examples for the unconscious determinants of behavior and antisocial personality changes caused by brain lesions in a wider psychological and social context, the paper argues for a cautious middle position: Evidence for an impending normative "neuro-revolution" is scarce and neuroscience may instead gradually improve legal practice in the long run, particularly where normative questions directly pertain to brain-related questions. In the conclusion the paper raises concerns that applying neuroscience methods about an individual's responsibility or dangerousness is premature at the present time and carries serious individual and societal risks. Putting findings from brain research in wider contexts renders them empirically investigable in a way that does not neglect psychological and social aspects of human mind and behavior.

From moral to legal judgment: the influence of normative context in lawyers and other academics.

Various kinds of normative judgments are an integral part of everyday life. We extended the scrutiny of social cognitive neuroscience into the domain of legal decisions, investigating two groups, lawyers and other academics, during moral and legal decision-making. While we found activation of brain areas comprising the so-called 'moral brain' in both conditions, there was stronger activation in the left dorsolateral prefrontal cortex and middle temporal gyrus particularly when subjects made legal decisions, suggesting that these were made in respect to more explicit rules and demanded more complex semantic processing. Comparing both groups, our data show that behaviorally lawyers conceived themselves as emotionally less involved during normative decision-making in general. A group × condition interaction in the dorsal anterior cingulate cortex suggests a modulation of normative decision-making by attention based on subjects' normative expertise.

FMRI in translation: the challenges facing real-world applications.

Functional neuroimaging has increased our understanding of human brain function tremendously and has become a standard tool in clinical and cognitive neuroscience research. We briefly review its methodological foundations and describe remaining challenges for translational research. The application of neuroimaging results to individual subjects, for example in predicting treatment response or determining the veracity of a statement, is limited by these challenges, in particular by the anatomical and statistical procedures commonly employed. We thus argue for sincere caution in the translation of functional neuroimaging to real-world applications.