Neuropsychiatric disorders such as drug addiction, depression and schizophrenia are often centrally implicated in public health challenges. These conditions impact the individuals affected and have widespread implications, contributing to related crises such as opioid epidemic, rising suicide rates and homelessness. Despite their influence, public health interventions frequently emphasise individual responsibility, overlooking the complex interplay of neurobiological and systemic factors that underpin these disorders. Current public health frameworks, such as the Nuffield Council on Bioethics’ intervention ladder, prioritise efforts (...) that encourage individual behaviour change. Paetkau critiques this emphasis on individual responsibility, emphasising the need to consider more systemic factors, such as social determinants of health, as targets of necessary intervention.1 We aim to reinforce Paetkau’s critique of the intervention ladder by introducing three neuropsychiatric case studies, each highlighting the limitations of an individual-based framework in addressing psychopathology-involved public health issues. We argue that conditions like addiction, depression and serious mental illness undermine the emphasis on individual responsibility in public health and policy interventions. To this end, neuroscience demonstrates that effective public health interventions necessitate a shift from the long-standing emphasis on individual responsibility towards more comprehensive, systems-level interventions. Opioid overdose deaths in the USA have sextupled since 1999, with over 100,000 deaths in 2023 alone.2 The opioid crisis has since remained one of the most pressing public …. (shrink)

Recent reports and papers on chimeric research highlight the promise of chimeric models of human neuropsychiatric disorders to ameliorate human suffering due to autism spectrum disorders, depression, and schizophrenia. These calls, however, typically do not acknowledge, much less address, criticisms of model creation and validation, or concerns about scientific conduct more generally. The ethical justification for the use of nonhuman animals in research depends on the production of benefits to humans based on such research. But the assessment (...) and production of benefits are highly uncertain and rife with both practical and conceptual challenges. This essay provides a general framework for classifying the benefits of biomedical research and then focuses on two factors that directly impact—and threaten—the production of knowledge in research that models neuropsychiatric disorders. (shrink)

Here we argue how Hoerl & McCormack's dual system proposal may change the current view about the neural correlates underlying temporal information processing. We also consider that the concept of the dual system may help characterize various timing disabilities in neuropsychiatric disorders from the new perspective.

Neuropsychiatric disorders introduce distinct challenges to clinical decision-making. Affected patients often experience impairments or absences in rationality, lucidity and cogni-emotional capacities, rendering it difficult for them to engage in the decision-making process. In turn, dynamics of the patient-physician relationship become strained, including when physicians employ bioethical principlism or moral case deliberation to arrive at ethically justified courses of action–both of which require sufficient communication and rationality that may be impaired or altogether absent in the presence of psychopathology. The (...) complexity of neuropsychiatric conditions therefore compels interrogation towards how ethics consultations are currently constructed and conducted when full communication or rational decision-making cannot be assumed. Delany et al, for example, present a robust, methodical framework for ethical deliberation.1 Such methodologies for facilitating ethical decision-making, although valuable in predominant contexts, assume full participant engagement and decision-making capacities (eg, independent moral agency). Neuropsychiatric disorders complicate this assumption, making it difficult for patients with limited decision-making capacity to engage meaningfully in proposed ethics consultations.2 This paper will explore how neuropsychiatric disorders complicate the assumptions of full participant engagement underlying ethical frameworks. It will argue that, by adapting ethics consultations to function as a ‘mental prosthesis’, clinicians can better navigate the ethical challenges posed by neuropsychiatric disorders, helping to ensure that patient autonomy is upheld even in cases of impaired cognitive …. (shrink)

Kafka's writings are frequently interpreted as representing the historical period of modernism in which he was writing. Little attention has been paid, however, to the possibility that his writings may reflect neural mechanisms in the processing of self during hypnagogic (i.e., between waking and sleep) states. Kafka suffered from dream-like, hypnagogic hallucinations during a sleep-deprived state while writing. This paper discusses reasons (phenomenological and neurobiological) why the self projects an imaginary double (autoscopy) in its spontaneous hallucinations and how Kafka's writings (...) help to elucidate the underlying cognitive and neural mechanisms. I further discuss how the proposed mechanisms may be relevant to understanding paranoid delusions in schizophrenia. Literature documents and records cognitive and neural processes of self with an intimacy that may be otherwise unavailable to neuroscience. To elucidate this approach, I contrast it with the apparently popularizing view that the symptoms of schizophrenia result from what has been called an operative (i.e., pre-reflective) hyper-reflexivity. The latter approach claims that pre-reflective self-awareness (diminished in schizophrenia) pervades all conscious experience (however, in a manner that remains unverifiable for both phenomenological and experimental methods). This contribution argues the opposite: the. (shrink)

Coronavirus disease 2019 (COVID-19) is likely to have long-term mental health effects on individuals who have recovered from COVID-19. Rightly, there is a global response for recognition and planning on how to deal with mental health problems for everyone impacted by the global pandemic. This does not just include COVID-19 patients but the general public and health care workers as well. There is also a need to understand the role of the virus itself in the pathophysiology of mental health (...) class='Hi'>disorders and longer-term mental health sequelae. Emerging evidence suggests that COVID-19 patients develop neurological symptoms such as headache, altered consciousness, and paraesthesia. Brain tissue oedema and partial neurodegeneration have also been observed in an autopsy. In addition, there are reports that the virus has the potential to cause nervous system damage. Together, these findings point to a possible role of the virus in the development of acute psychiatric symptoms and long-term neuropsychiatric sequelae of COVID-19. The brain pathologies associated with COVID-19 infection is likely to have a long-term impact on cognitive processes. Evidence from other viral respiratory infections, such as severe acute respiratory syndrome (SARS), suggests a potential development of psychiatric disorders, long-term neuropsychiatric disorders, and cognitive problems. In this paper, we will review and evaluate the available evidence of acute and possible long-term neuropsychiatric manifestations of COVID-19. We will discuss possible pathophysiological mechanisms and the implications this will have on preparing a long-term strategy to monitor and manage such patients. (shrink)

Deep Brain Stimulation (DBS) represents a key area of neuromodulation that has gained wide adoption for the treatment of neurological and experimental testing for psychiatric disorders. It is associated with specific therapeutic effects based on the precision of an evolving mechanistic neuroscientific understanding. At the same time, there are obstacles to achieving symptom relief because of the incompleteness of such an understanding. These obstacles are at least in part based on the complexity of neuropsychiatric disorders and the (...) incompleteness of DBS devices to represent prosthetics that modulate the breadth of pathological processes implicated in these disorders. Neuroprostheses, such as an implanted DBS system, can have vast effects on subjects in addition to the specific neuropsychiatric changes they are intended to produce. These effects largely represent blind spots in the current debate on neuromodulation. Anthropological accounts can illustrate the broad existential dimensions of patients’ illness and responses to neural implants. In combination with current neuroscientific understanding, neuropsychiatric anthropology may illuminate the possibilities and limits of neurodevices as technical “world enablers”. (shrink)

Considerable heterogeneity among pediatric chronic pain patients may at least partially explain the variability seen in the response to behavioral therapies. The current study tested whether autistic traits and attention-deficit/hyperactivity disorder symptoms in a clinical sample of children and adolescents with chronic pain are associated with socioemotional and functional impairments and response to acceptance and commitment therapy treatment, which has increased psychological flexibility as its core target for coping with pain and pain-related distress. Children and adolescents aged 8–18 years were (...) recruited. Patients and their parents completed questionnaires pre- and post-ACT of 17 sessions. Correlational analyses and mixed-effects models were used to assess the role of autistic traits and ADHD symptoms in pretreatment functioning and ACT-treatment response. Outcome variables were degree to which pain interfered with daily activities, socioemotional functioning, psychological inflexibility, and pain intensity. Autistic traits and ADHD symptoms, pain frequency, and pain duration were measured at pretreatment only. Higher autistic traits were associated with greater pain interference, higher depression, and greater psychological inflexibility. Higher ADHD symptomatology was associated with greater pretreatment pain interference, lower emotional functioning, greater depression, and longer duration of pain. Across patients, all outcome variables, except for sleep disturbances and school functioning, significantly improved from pre- to post-ACT. Higher autistic traits were associated with greater pre- to post-ACT improvements in emotional functioning and sleep disturbance and non-significant improvements in pain interference. ADHD symptomatology was not associated with treatment outcome. The current results showed that neuropsychiatric symptoms in pediatric chronic pain patients are associated with lower functioning, particularly pain interfering with daily life and lower socioemotional functioning. The results suggest that not only pediatric chronic pain patients low in neuropsychiatric symptoms may benefit from ACT, but also those high in autism traits and ADHD symptoms. With the present results in mind, pediatric chronic pain patients higher in autistic traits may actually derive extra benefit from ACT. Future research could assess whether increased psychological flexibility, the core focus of ACT, enabled those higher in autism traits to cope relatively better with pain-related distress and thus to gain more from the treatment, as compared to those lower in autism traits. Moreover, to address specific effects of ACT, inclusion of an appropriate control group is key. (shrink)

The first clinical symptoms focused on the presentation of coronavirus disease 2019 have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins.Methods: Available 11 of the 29 SARS-CoV-2 proteins’ structures have been extracted from Protein Data (...) Bank. HMI-PRED, a recently developed web server for structural PREDiction of protein-protein interactions between host and any microbial species, was used to find the “interface mimicry” through which the microbial proteins hijack host binding surfaces. Classification of the found interactions was conducted using the PANTHER Classification System.Results: Predicted Human-SARS-CoV-2 protein interactions have been extensively compared with the literature. Based on the analysis of the molecular functions, cellular localizations and pathways related to human proteins, SARS-CoV-2 proteins are found to possibly interact with human proteins linked to synaptic vesicle trafficking, endocytosis, axonal transport, neurotransmission, growth factors, mitochondrial and blood-brain barrier elements, in addition to its peripheral interactions with proteins linked to thrombosis, inflammation and metabolic control.Conclusion: SARS-CoV-2-human protein interactions may lead to the development of delirium, psychosis, seizures, encephalitis, stroke, sensory impairments, peripheral nerve diseases, and autoimmune disorders. Our findings are also supported by the previous in vivo and in vitro studies from other viruses. Further in vivo and in vitro studies using the proteins that are pointed here, could pave new targets both for avoiding and reversing neuropsychiatric presentations. (shrink)

The target article by Charney on behavior genetics/genomics discusses how numerous molecular factors can inform heritability estimations and genetic association studies. These factors find application in the search for genes for behavioral phenotypes, including neuropsychiatric disorders. We elaborate upon how single causal factors can generate multiple phenotypes, and discuss how multiple causal factors may converge on common neurodevelopmental mechanisms.

This article gives an overview of what we can learn about face perception from studying its disorders. The term “disorders” is broadly interpreted to include acquired brain injury and disease, neurodevelopmental differences, and neuropsychiatric problems. The article examines the reasons for various opinions about what can be learnt from disorders, ranging from the entire spectrum from “nothing that isn't misleading” to “everything worth knowing.” Cognitive neuropsychology typically operates in a unique way, in which the emphasis is (...) on detailed analysis of individual patients with theoretically interesting impairments. The article then highlights a number of the assumptions that get made, explains why things are often complicated, and emphasizes the value of a pragmatic “converging operations” approach in which evidence from disorders of face perception is brought together with other sources of data and theory. (shrink)

The generation of three-dimensional cerebral organoids from human-induced pluripotent stem cells (hPSC) has facilitated the investigation of mechanisms underlying several neuropsychiatric disorders, including stress-related disorders, namely major depressive disorder and post-traumatic stress disorder. Generating hPSC-derived neurons, cerebral organoids, and even assembloids (or multi-organoid complexes) can facilitate research into biomarkers for stress susceptibility or resilience and may even bring about advances in personalized medicine and biomarker research for stress-related psychiatric disorders. Nevertheless, cerebral organoid research does not come (...) without its own set of ethical considerations. With increased complexity and resemblance to in vivo conditions, discussions of increased moral status for these models are ongoing, including questions about sentience, consciousness, moral status, donor protection, and chimeras. There are, however, unique ethical considerations that arise and are worth looking into in the context of research into stress and stress-related disorders using cerebral organoids. This paper provides stress research-specific ethical considerations in the context of cerebral organoid generation and use for research purposes. The use of stress research as a case study here can help inform other practices of in vitro studies using brain models with high ethical considerations. (shrink)

Philosophers have long been involved in the pursuit of a goal shared by researchers in psychiatry and the cognitive sciences: understanding the relationship between the functioning of the human mind and human well-being or suffering. For this reason there is a very large area of overlap between philosophical and psychiatric research. The overlap is particularly significant in the domain of practical ethics, which is concerned with understanding the moral dimension of policies and actions in the real world. This chapter reviews (...) two distinct domains in which psychiatry and practical ethics overlap. First, issues in practical ethics arise out of new advances in psychopharmacology, including clinical and non-clinical use of new antidepressants drugs, the clinical use of placebo medications, and psychiatric drugs which enhance human cognition; these issues are frequently grouped under the banner of "neuroethics." Second, the understanding of fundamental questions in moral philosophy is being driven forward by evidence from psychology and psychiatry. Evidence from autism and the personality disorders is shedding light on the nature of moral motivation, while evidence from addiction and compulsion is generating progress in understanding moral responsibility. Finally, some areas are highlighted in which the science of psychiatry may benefit from the application of existing work in moral philosophy and practical ethics. (shrink)

Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease can lead to the development of neuropsychiatric symptoms. These can include harmful changes in mood and behaviour that alienate family members and raise ethical questions about personal responsibility for actions committed under stimulation-dependent mental states. Qualitative interviews were conducted with twenty participants following subthalamic DBS at a movement disorders centre, in order to explore the meaning and significance of stimulation-related neuropsychiatric symptoms amongst a purposive (...) sample of persons with PD and their spousal caregivers. Interview transcripts underwent inductive thematic analysis. Clinical and experiential aspects of post-DBS neuropsychiatric symptoms were identified. Caregivers were highly burdened by these symptoms and both patients and caregivers felt unprepared for their consequences, despite having received information prior to DBS, desiring greater family and peer engagement prior to neurosurgery. Participants held conflicting opinions as to whether emergent symptoms were attributable to neurostimulation. Many felt that they reflected aspects of the person’s “real” or “younger” personality. Those participants who perceived a close relationship between stimulation changes and changes in mental state were more likely to view these symptoms as inauthentic and uncontrollable. Unexpected and troublesome neuropsychiatric symptoms occurred despite a pre-operative education programme that was delivered to all participants. This suggests that such symptoms are difficult to predict and manage even if best practice guidelines are followed by experienced centres. Further research aimed at predicting these complications may improve the capacity of clinicians to tailor the consent process. (shrink)

Opioid use disorder rarely presents as a unitary psychiatric condition, and the comorbid symptoms likely depend upon the diverse risk factors and mechanisms by which OUD can arise. These factors are heterogeneous and include genetic predisposition, exposure to prescription opioids, and environmental risks. Crucially, one key environmental risk factor for OUD is early life adversity. OUD and other substance use disorders are widely considered to derive in part from abnormal reward circuit function, which is likely also implicated in comorbid (...) mental illnesses such as depression, bipolar disorder, and schizophrenia. ELA may disrupt reward circuit development and function in a manner predisposing to these disorders. Here, we describe new findings addressing the effects of ELA on reward circuitry that lead to OUD and comorbid disorders, potentially via shared neural mechanisms. We discuss some of these OUD-related problems in both humans and animals. We also highlight the increasingly apparent, crucial contribution of biological sex in mediating the range of ELA-induced disruptions of reward circuitry which may confer risk for the development of OUD and comorbid neuropsychiatric disorders. (shrink)

Deep brain stimulation — a novel surgical procedure — is emerging as a treatment of last resort for people diagnosed with neuropsychiatric disorders such as severe obsessive-compulsive disorder. The US Food and Drug Administration granted a so-called humanitarian device exemption to allow patients to access this intervention, thereby removing the requirement for a clinical trial of the appropriate size and statistical power. Bypassing the rigors of such trials puts patients at risk, limits opportunities for scientific discovery, and gives (...) device manufacturers unique marketing opportunities. We argue that Congress and federal regulators should revisit the humanitarian device exemption to ensure that it is not used to sidestep careful research that can offer valuable data with appropriate patient safeguards. (shrink)

The metamorphosis of human beings into wolves is well known in mythology, legend, and scripture, and has been extensively surveyed in history, theology, and literature. Werewolf cases have attracted the attention of both ancient and modern physicians, particularly during the development of modern psychiatry and behavioral neurology. Some writers have suggested that lycanthropes suffered from schizophrenia or had intentionally or involuntarily ingested hallucinogens. Hysteria and affective disorder, either mania or intense depression, could also be invoked as causes. Lycanthropy has often (...) been linked with, and sometimes treated by, henbane and nightshade, and its manifestations could be explained in terms of atropinic delirium. Discoloration of teeth and urine, bizarre behavior, nocturnal wandering, and episodic skin and facial changes have suggested a role for porphyria in the werewolf transformation. Through many historical periods and cultures, persons believed to be werewolves have reportedly exhibited alterations in consciousness, depersonalization and derealization, acute anxiety and agitation, preoccupation with demonic possession, and compulsive or perseverative behavior, sometimes of a violent, sexually deviant or impulsive nature. Such features of werewolf behavior might also be explained by ictal and interictal manifestations of complex partial seizures, or as symptoms of the episodic dyscontrol syndrome associated with frontal lobe or limbic system disease or injury. Lycanthropy was often considered a manifestation of demonic possession or a consequence or indication of participation in necromancy. As such, self-proclaimed or suspected werewolves were often persecuted along with other practitioners of the black arts. It is generally believed that such persecution represented the last efflorescence of medieval demonology, but it has also been suggested that clinical description of illnesses of diabolical origin was part of the evolution of Renaissance medicine from the Galenic past toward the scientifically-based future. (shrink)

We provide an introduction to network theory, evidence to support a connection between molecular network structure and neuropsychiatric disease, and examples of how network approaches can expand our knowledge of the molecular bases of these diseases. Without systematic methods to derive their biological meanings and inter‐relatedness, the many molecular changes associated with neuropsychiatric disease, including genetic variants, gene expression changes, and protein differences, present an impenetrably complex set of findings. Network approaches can potentially help integrate and reconcile these (...) findings, as well as provide new insights into the molecular architecture of neuropsychiatric diseases. Network approaches to neuropsychiatric disease are still in their infancy, and we discuss what might be done to improve their prospects. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Subjective Knowledge, Mental Disorders, and MedsHow to Parse the EquationMark D. Rego (bio)Keywordspsychopathology, antidepressants, suicidality, subjective experience, pre-reflectiveA few weeks, ago I was walking down the hall to my office when I spotted my brother-in-law coming the other way. This was odd on two accounts. First, he lives in Kentucky (I am in Connecticut) and second, he is at least a foot taller than the man in my (...) hallway. Nonetheless, I struggled to figure out why he was there. The resemblance was so striking it took me a minute or two to convince myself it was not him. Even after such convincing, the feeling that it was him remained.Later, I imagined that had I just returned from a crack cocaine den I would have been hypervigilant, if not paranoid, and consequently would be certain that my brother-in-law had arrived unannounced. Furthermore, I would probably assume that he was up to no good.How did I retain a strong feeling of recognition, the feeling that maybe it was really him, when I already concluded otherwise? And why, were I on crack cocaine, would the obvious facts be useless in rendering a decision about the identity of the man in the hall? Last, why would the post-cocaine man in the hall become a nefarious brother-in-law rather than a benign one?If I just computed some symbols to figure this out, wouldn't the feeling have gone away? If I activated a brother-in-law neural network, how did I come to acquire an evil brother-in-law neural network? And why wouldn't that go away either?In his article in this issue of Philosophy, Psychiatry, & Psychology, Hadreas looks at questions like these through the prism of before and after effects of people treated with selective serotonin reuptake inhibitors (SSRIs). Hadreas investigates the implications of a straightforward recomputation of self-awareness when treated with these medicines and finds such approaches unsatisfying and incomplete in their explanatory power. (My example looks at a type of awareness, but not specifically self-awareness, as does Hadreas. Furthermore, my paradigm asks about computational conclusions using language more common in psychiatric literature, whereas Hadreas uses standard philosophical terms. Although not isomorphic, I believe the interchange of the two remains true to the issues Hadreas is addressing). [End Page 57]In my example, there is clearly something else going on than the incorrect arrangement of symbols or the misfiring of nodes in a network that influences how I feel and what I think. Neither reason nor empiricism seem to serve me well here. Hadreas utilizes Husserl to begin to unpeel the layers of self-awareness and self-states that intermix to form the shifts and contradictions which are so common in psychiatric treatment (and in common experience as I describe).This is a welcome reckoning; the psychiatric literature is overflowing with unquestioned premises about the neuropsychiatric correlates of reason and empirical approaches (described more as computation and neural networks in the literature—again, not strictly analogous, but the same criticisms apply) Hadreas is critical of. Unfortunately, Hadreas has navigated through a sea of highly questionable assumptions about the psychopharmacology of depression to illustrate his points. This is due in large part to the common practice of consulting literary narratives and critics rather than one of immersion in the literature as a whole and the daily life of patients and active clinicians. He arrived at his destination despite this, because many of these details did not affect his particular analysis. However, to look forward to a continuation of this work and clarify some important issues I devote most of my commentary to these issues. The points I raise are more extensively discussed in a previous edition of this journal (Rego 2005).Affect to Reason ShiftLet's begin with the idea that SSRIs work by dampening emotions. An extension of this idea is that they dampen negative emotions and strengthen positive ones like assertiveness, confidence, and optimism. An even further development in this direction is that, by dampening strong emotions, cognitive enhancement takes place with SSRI treatment. A summary observation then is that SSRIs facilitate... (shrink)

There is a steadily growing literature on the role of the immune system in psychiatric disorders. So far, these advances have largely taken the form of correlations between specific aspects of inflammation (e.g. blood plasma levels of inflammatory markers, genetic mutations in immune pathways, viral or bacterial infection) with the development of neuropsychiatric conditions such as autism, bipolar disorder, schizophrenia and depression. A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? To address this (...) would require a step back from a historical mind–body dualism that has created such a dichotomy. We propose three contributions of active inference when addressing this question: translation, unification, and simulation. To illustrate these contributions, we consider the following questions. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people? Does false inference at an immunological level alter the message passing at a psychological level (or vice versa) through a principled exchange between the two systems? (shrink)

Generalized anxiety disorder can cause significant socioeconomic burden and daily life dysfunction; hence, therapeutic intervention through early detection is important. This study was the final stage of a 3-year anxiety screening tool development project that evaluated the psychometric properties and diagnostic screening utility of the Mental Health Screening Tool for Anxiety Disorders, which measures GAD. A total of 527 Koreans completed online and offline versions of the MHS: A, Beck Anxiety Inventory, Generalized Anxiety Disorder-7, and Penn State Worry Questionnaire. (...) The participants had an average age of 38.6 years and included 340 females. Participants were also administered the Mini-International Neuropsychiatric Interview. Internal consistency, convergent/criterion validity, item characteristics, and test information were assessed based on the item response theory, and a factor analysis and cut-off score analyses were conducted. The MHS: A had good internal consistency and good convergent validity with other anxiety scales. The two versions of the MHS: A were nearly identical. It had a one-factor structure and showed better diagnostic accuracy for GAD detection than the GAD-7 and BAI. The IRT analysis indicated that the MHS: A was most informative as a screening tool for GAD. The MHS: A can serve as a clinically useful screening tool for GAD in Korea. Furthermore, it can be administered both online and offline and can be flexibly used as a brief mental health screener, especially with the current rise in telehealth. (shrink)

Mitochondrial ATP synthesis, calcium buffering, and trafficking affect neuronal function and survival. Several genes implicated in mitochondrial functions map within the genomic region associated with 22q11.2 deletion syndrome (22q11DS), which is a key genetic cause of neuropsychiatric diseases. Although neuropsychiatric diseases impose a serious health and economic burden, their etiology and pathogenesis remain largely unknown because of the dearth of valid animal models and the challenges in investigating the pathophysiology in neuronal circuits. Mouse models of 22q11DS are becoming (...) valid tools for studying human psychiatric diseases, because they have hemizygous deletions of the genes that are deleted in patients and exhibit neuronal and behavioral abnormalities consistent with neuropsychiatric disease. The deletion of some 22q11DS genes implicated in mitochondrial function leads to abnormal neuronal and synaptic function. Herein, we summarize recent findings on mitochondrial dysfunction in 22q11DS and extend those findings to the larger context of schizophrenia and other neuropsychiatric diseases. (shrink)

Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms may be either of neurologic origin, for example, Parkinson's disease, or of psychiatric origin, for example, catatonia, leading to a so-called “conflict of paradigms.” Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociation between origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinson's (...) disease and catatonia may be accounted for by distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrent motor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting “horizontal modulation” of cortico-cortical relation. Furthermore, alteration in “top-down modulation” reflecting “vertical modulation” of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinson's disease, in contrast, can be characterized by predominant motor symptoms. Motor symptoms may be accounted for by altered “bottom-up modulation” between dopaminergic mediated deficits in striatum and premotor/motor cortex. Clinical similarities between Parkinson's disease and catatonia with respect to akinesia may be related with involvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be related with involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modulation – “vertical” and “horizontal” modulation, respectively. Key Words: Bottom-up modulation; catatonia; horizontal modulation; Parkinson's disease; top-down modulation; vertical modulation. (shrink)

Background: There has for some time now been recognition that there was a relationship between exceptional creative talent and mental disorder. The works of Andreasen (2008) and others in this area have been very significant. However, most of the research has been carried out in USA and Europe. Very little has come out of Africa on the subject. Aim : To survey the beliefs of different groups within an African society, concerning the possibility of a relationship between creative talent and (...) mental disorder. To assess creativity within a community of people with a formal diagnosis of mental disorder. Materials and Methods: Some of the mythology of the Yoruba was examined for content, concerning the behaviour of certain notable individuals and the existence of psychopathology based on modern-day criteria. The beliefs of members of the general public and mental health professionals concerning the existence of a relationship between creative talent and psychopathology were surveyed using a questionnaire designed for the project. A sample of patients with formal diagnoses of affective disorder or schizophrenia drawn from two units, the Lagos State University Teaching Hospital and the Federal Neuropsychiatric Hospital Yaba, were assessed for 'Creativity.' Results : Although there are notable 'eccentric' figures in local mythology, the overwhelming majority of the people surveyed do not believe there is any relationship between creativity and mental illness. They however believe that engaging in creative activities helps the mentally ill to recover from illness. The mental health professionals, who were clinical psychologists and psychiatrists, had a significant minority who believed that a relationship does exist, and they also strongly assert that creative activity has a therapeutic effect for the mentally ill. A survey of in-patients diagnosed with schizophrenia and affective disorder failed to show a significant difference in the creativity of the two populations, as measured by the originality score of the Rorschach scale. The survey of patients is inconclusive, based on small sample size (ten patients with a diagnosis of schizophrenia, ten with bipolar affective disorder.). The linkage between formal mental disorder is only recognised by a significant minority of mental health professionals. A significant proportion of the population believe that creative activity aids recovery from mental illness. More research is required into this important subject in Africa. (shrink)

Bioethics needs an elaborated concept of autonomy based on empirical knowledge about the prerequisites of the capacity of autonomy. Whereas Beauchamp and Childress, and many other bioethicists have discussed social influences on the capacity of autonomy in depth, neurobiological influences have received less attention. A comprehensive concept of autonomy should consider both social and biological factors that can diminish the capacity of autonomy. This article focuses on neurobiological influences that can reduce the capacity of autonomy. The thesis of this article (...) is that the integration of neuropsychiatric knowledge into the concept of autonomy is essential for evaluating demands for harmful medical treatments which might be caused by a brain disease, and deciding on involuntary treatments of patients who suffer from substantial lack of autonomy due to neuropsychiatric disorders. Diametrically opposed to such a comprehensive concept of the capacity of autonomy is the concept of ‘liberty of illness’. In Germany, this concept is supported not only by anti-psychiatric groups but also by the Federal Constitutional Court. Several real cases demonstrate how the brain can be ‘hijacked’ by parasites, antibodies or technical devices. Applying the concept of ‘liberty of illness’ to persons whose decision-making capacity is severely affected by neuropsychiatric disorders is cynical. These patients neither chose their disease nor would refuse effective treatment if their will was not disturbed by the disease. Respect for autonomy should be understood as the positive obligation to save, support or restore the biological prerequisites of the capacity for autonomous decision-making. (shrink)

In this paper we discuss the two-system framework, examine its strengths, point out a fundamental weakness concerning the unity of conscious experience, and then propose a new hypothesis that avoids that weakness and other related concerns. According to our strong emergence hypothesis, what emerges are not merely mental properties in specialized, distributed neural areas, but also a new, irreducibly singular entity that functions in a recurrent manner to integrate its mental properties and to rewire its brain. We argue that the (...) former function is suggested, in part, by the effects of anesthetics on sensory integration, and that the latter function is suggested by evidence garnered from the neuroscience of mindfulness, constraint-induced movement therapy for stroke, and neuroimaging data surrounding mental illness. We then discuss how our strong emergence hypothesis relates to the description and treatment of neuropsychiatric disorders. Finally, potential objections are addressed. (shrink)

ABSTRACT I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments. INTRODUCTION In contrast to the classic model of randomized-control trials, often with a large number of (...) subjects enrolled, precision medicine attempts to optimize therapeutic outcomes by focusing on the individual.[i] A recent publication highlights the strengths and weakness of both traditional evidence-based medicine and precision medicine.[ii] Plus, it outlines a tension in the shift from evidence-based medicine’s inductive reasoning style (the collection of data to postulate general theories) to precision medicine’s abductive reasoning style (the generation of an idea from the limited data available).[iii] The paper’s main example is the application of precision medicine for the treatment of cancer.[iv] I argue that this examination and appreciation for the shift to abductive reasoning should be extended to the intersection of neuroscience and novel brain-computer interfaces too. As the name suggests, brain-computer interfaces are a significant advancement in neurotechnology that directly connects someone’s brain to external or implanted devices.[v] Among the various kinds of brain-computer interfaces, adaptive deep brain stimulation devices require numerous personalized adjustments to their settings during the implantation and computation stages in order to provide adequate relief to patients with treatment-resistant disorders. What makes these devices unique is how adaptive deep brain stimulation integrates a sensory component to initiate the stimulation. While not commonly at the level of sophistication as self-supervising or generative large language models,[vi] they currently allow for a semi-autonomous form of neuromodulation. This paper highlights the implications of applying abductive reasoning to personalized implantable neurotechnologies. Then, it explores whether abductive reasoning is sufficient to justify insurance coverage for devices absent widespread clinical trials, which are better applied to one-size-fits-all treatments.[vii] ANALYSIS I. The State of Precision Medicine in Oncology and the Epistemological Shift While a thorough overview of precision medicine for the treatment of cancer is beyond the scope of this article, its practice can be roughly summarized as identifying clinically significant characteristics a patient possesses (e.g., genetic traits) to land on a specialized treatment option that, theoretically, should benefit the patient the most.[viii] However, in such a practice of stratification patients fall into smaller and smaller populations and the quality of evidence that can be applied to anyone outside these decreases in turn.[ix] As inductive logic helps to articulate, the greater the number of patients that respond to a particular therapy the higher the probability of its efficacy. By straying from this logical framework, precision medicine opens the treatment of cancer to more uncertainty about the validity of these approaches to the resulting disease subcategories.[x] Thus, while contemporary medical practices explicitly describe some treatments as “personalized”, they ought not be viewed as inherently better founded than other therapies.[xi] A relevant contemporary case of precision medicine out of Norway focuses on the care of a patient with cancer between the ventricles of the heart and esophagus, which had failed to respond to the standard regimen of therapies over four years.[xii] In a last-ditch effort, the patient elected to pay out-of-pocket for an experimental immunotherapy (nivolumab) at a private hospital. He experienced marked improvements and a reduction in the size of the tumor. Understandably, the patient tried to pursue further rounds of nivolumab at a public hospital. However, the hospital initially declined to pay for it given the “lack of evidence from randomised clinical trials for this drug relating to this [patient’s] condition.”[xiii] In rebuttal to this claim, the patient countered that he was actually similar to a subpopulation of patients who responded in “open‐label, single arm, phase 2 studies on another immune therapy drug” (pembrolizumab).[xiv] Given this interpretation of the prior studies and the patient’s response, further rounds of nivolumab were approved. Had the patient not had improvements in the tumor’s size following a round of nivolumab, then pembrolizumab’s prior empirical evidence in isolation would have been insufficient, inductively speaking, to justify his continued use of nivolumab.[xv] The case demonstrates a shift in reasoning from the traditional induction to abduction. The phenomenon of ‘cancer improvement’ is considered causally linked to nivolumab and its underlying physiological mechanisms.[xvi] However, “the weakness of abductions is that there may always be some other better, unknown explanation for an effect. The patient may for example belong to a special subgroup that spontaneously improves, or the change may be a placebo effect. This does not mean, however, that abductive inferences cannot be strong or reasonable, in the sense that they can make a conclusion probable.”[xvii] To demonstrate the limitations of relying on the abductive standard in isolation, commentators have pointed out that side effects in precision medicine are hard to rule out as being related to the initial intervention itself unless trends from a group of patients are taken into consideration.[xviii] As artificial intelligence (AI) assists the development of precision medicine for oncology, this uncertainty ought to be taken into consideration. The implementation of AI has been crucial to the development of precision medicine by providing a way to combine large patient datasets or a single patient with a large number of unique variables with machine learning to recommend matches based on statistics and probability of success upon which practitioners can base medical recommendations.[xix] The AI is usually not establishing a causal relationship[xx] – it is predicting. So, as AI bleeds into medical devices, like brain-computer interfaces, the same cautions about using abductive reasoning alone should be carried over. II. Responsive Neurostimulation, AI, and Personalized Medicine Like precision medicine in cancer treatment, computer-brain interface technology similarly focuses on the individual patient through personalized settings. In order to properly expose the intersection of AI, precision medicine, abductive reasoning, and implantable neurotechnologies, the descriptions of adaptive deep brain stimulation systems need to deepen.[xxi] As a broad summary of adaptive deep brain stimulation, to provide a patient with the therapeutic stimulation, a neural signal, typically referred to as a local field potential,[xxii] must first be detected and then interpreted by the device. The main adaptive deep brain stimulation device with premarket approval, the NeuroPace Responsive Neurostimulation system, is used to treat epilepsy by detecting and storing “programmer-defined phenomena.”[xxiii] Providers can optimize the detection settings of the device to align with the patient’s unique electrographic seizures as well as personalize the reacting stimulation’s parameters.[xxiv] The provider adjusts the technology based on trial and error. One day machine learning algorithms will be able to regularly aid this process in myriad ways, such as by identifying the specific stimulation settings a patient may respond to ahead of time based on their electrophysiological signatures.[xxv] Either way, with AI or programmers, adaptive neurostimulation technologies are individualized and therefore operate in line with precision medicine rather than standard treatments based on large clinical trials. Contemporary neurostimulation devices are not usually sophisticated enough to be prominent in AI discussions where the topics of neural networks, deep learning, generative models, and self-attention dominate the conversation. However, implantable high-density electrocorticography arrays (a much more sensitive version than adaptive deep brain stimulation systems use) have been used in combination with neural networks to help patients with neurologic deficits from a prior stroke “speak” through a virtual avatar.[xxvi] In some experimental situations, algorithms are optimizing stimulation parameters with increasing levels of independence.[xxvii] An example of neurostimulation that is analogous to the use of nivolumab in Norway surrounds a patient in the United States who was experiencing both treatment-resistant OCD and temporal lobe epilepsy.[xxviii]Given the refractory nature of her epilepsy, implantation of an adaptive deep brain stimulation system was indicated. As a form of experimental therapy, her treatment-resistant OCD was also indicated for the off-label use of an adaptive deep brain stimulation set-up. Another deep brain stimulation lead, other than the one implanted for epilepsy, was placed in the patient’s right nucleus accumbens and ventral pallidum region given the correlation these nuclei had with OCD symptoms in prior research. Following this, the patient underwent “1) ambulatory, patient-initiated magnet-swipe storage of data during moments of obsessive thoughts; (2) lab-based, naturalistic provocation of OCD-related distress (naturalistic provocation task); and (3) lab-based, VR [virtual reality] provocation of OCD-related distress (VR provocation task).”[xxix] Such signals were used to identify when to deliver the therapeutic stimulation in order to counter the OCD symptoms. Thankfully, following the procedure and calibration the patient exhibited marked improvements in their OCD symptoms and recently shared her results publicly.[xxx] In both cases, there is a similar level of abductive justification for the efficacy of the delivered therapy. In the case study in which the patient was treated with adaptive deep brain stimulation, they at least had their neural activity tested in various settings to determine the optimum parameters for treatment to avoid them being based on guesswork. Additionally, the adaptive deep brain stimulation lead was already placed before the calibration trials were conducted, meaning that the patient had already taken on the bulk of the procedural risk before the efficacy could be determined. Such an efficacy test could have been replicated in the first patient’s cancer treatment, had it been biopsied and tested against the remaining immunotherapies in vitro. Yet, in the case of cancer with few options, one previous dose of a drug that appeared to work on the patient may justify further doses. However, as the Norwegian case presents, corroboration with known responses to a similar drug (from a clinical trial) could be helpful to validate the treatment strategy. (It should be noted that both patients were resigned to these last resort options regardless of the efficacy of treatment.) There are some elements of inductive logic seen with adaptive deep brain stimulation research in general. For example, abductively the focus could be that patient X’s stimulation parameters are different from patient Y’s and patient Z’s. In contrast, when grouped as subjects who obtained personalized stimulation, patients X, Y, and Z demonstrate an inductive aspect to this approach’s safety and/or efficacy. The OCD case holds plenty of abductive characteristics in line with precision medicine’s approach to treating cancer and as more individuals try the method, there will be additional data. With the gradual integration of AI into brain-computer interfaces in the name of efficacy, this reliance on abduction will continue, if not grow, over time. Moving forward, if a responsive deep brain stimulation treatment is novel and individualized (like the dose of nivolumab) and there is some other suggestion of efficacy (like clinical similarities to other patients in the literature), then it may justify insurance coverage for the investigative intervention, absent other unrelated reasons to deny it. III. Ethical Implications and Next Steps While AI’s use in oncology and neurology is not yet as prominent as its use in other fields (e.g., radiology), it appears to be on the horizon for both.[xxxi] AI can be found in both the functioning of the neurotechnologies as well as the implementation of precision medicine. The increasing use of AI may serve to further individualize both oncologic and neurological therapies. Given these implications and the handful of publications cited in this article, it is important to have a nuanced evaluation of how these treatments, which heavily rely on abductive justification, ought to be managed. The just use an abductive approach may be difficult as AI infused precision medicine is further pursued. At baseline, such technology relies on a level of advanced technology literacy among the general public and could exclude populations who lack access to basic technological infrastructure or know-how from participation.[xxxii] Even among nations with adequate infrastructure, as more patients seek out implantable neurotechnologies, which require robust healthcare resources, the market will favor patient populations that can afford this complex care.[xxxiii] If patients already have the means to pay for an initial dose/use of a precision medicine product out of pocket, should insurance providers be required to cover subsequent treatments?[xxxiv] That is, if a first dose of a cancer drug or a deep brain stimulator over its initial battery life is successful, patients may feel justified in having the costs of further treatments covered. The Norwegian patient’s experience implies there is a precedent for the idea that some public insurance companies ought to cover successful cancer therapies, however, insurance companies may not all see themselves as obligated to cover neurotechnologies that rely on personalized settings or that are based on precision/abductive research more than on clinical trials. CONCLUSION The fact that the cases outlined above rely on abductive style of reasoning implies that there may not be as strong a justification for coverage by insurance, as they are both experimental and individualized, when compared to the more traditional large clinical trials in which groups have the same or a standardized protocol (settings/doses). If a study is examining the efficacy of a treatment with a large cohort of patients or with different experimental groups/phases, insurance companies may conclude that the resulting symptom improvements are more likely to be coming from the devices themselves. A preference for inductive justification may take priority when ruling in favor of funding someone’s continued use of an implantable neurostimulator. There are further nuances to this discussion surrounding the classifications of these interventions as research versus clinical care that warrant future exploration, since such a distinction is more of a scale[xxxv] than binary and could have significant impacts on the “right-to-try” approach to experimental therapies in the United States.[xxxvi] Namely, given the inherent limitations of conducting large cohort trials for deep brain stimulation interventions on patients with neuropsychiatric disorders, surgically innovative frameworks that blend abductive and inductive methodologies, like with sham stimulation phases, have traditionally been used.[xxxvii] Similarly, for adaptive brain-computer interface systems, if there are no large clinical trials and instead only publications that demonstrate that something similar worked for someone else, then, in addition to the evidence that the first treatment/dose worked for the patient in question, the balance of reasoning would be valid and arguably justify insurance coverage. As precision approaches to neurotechnology become more common, frameworks for evaluating efficacy will be crucial both for insurance coverage and for clinical decision making. ACKNOWLEDGEMENT This article was originally written as an assignment for Dr. Francis Shen’s “Bioethics & AI” course at Harvard’s Center for Bioethics. I would like to thank Dr. Shen for his comments as well as my colleagues in the Lázaro-Muñoz Lab for their feedback. - [i] Jonathan Kimmelman and Ian Tannock, “The Paradox of Precision Medicine,” Nature Reviews. Clinical Oncology 15, no. 6 (June 2018): 341–42, https://doi.org/10.1038/s41571-018-0016-0. [ii] Henrik Vogt and Bjørn Hofmann, “How Precision Medicine Changes Medical Epistemology: A Formative Case from Norway,” Journal of Evaluation in Clinical Practice 28, no. 6 (December 2022): 1205–12, https://doi.org/10.1111/jep.13649. [iii] David Barrett and Ahtisham Younas, “Induction, Deduction and Abduction,” Evidence-Based Nursing 27, no. 1 (January 1, 2024): 6–7, https://doi.org/10.1136/ebnurs-2023-103873. [iv] Vogt and Hofmann, “How Precision Medicine Changes Medical Epistemology,” 1208. [v] Wireko Andrew Awuah et al., “Bridging Minds and Machines: The Recent Advances of Brain-Computer Interfaces in Neurological and Neurosurgical Applications,” World Neurosurgery, May 22, 2024, S1878-8750(24)00867-2, https://doi.org/10.1016/j.wneu.2024.05.104. [vi] Mark Riedl, “A Very Gentle Introduction to Large Language Models without the Hype,” Medium (blog), May 25, 2023, https://mark-riedl.medium.com/a-very-gentle-introduction-to-large-language-models-without-the-hype-5 f67941fa59e. [vii] David E. Burdette and Barbara E. Swartz, “Chapter 4 - Responsive Neurostimulation,” in Neurostimulation for Epilepsy, ed. Vikram R. Rao (Academic Press, 2023), 97–132, https://doi.org/10.1016/B978-0-323-91702-5.00002-5. [viii] Kimmelman and Tannock, 2018. [ix] Kimmelman and Tannock, 2018. [x] Simon Lohse, “Mapping Uncertainty in Precision Medicine: A Systematic Scoping Review,” Journal of Evaluation in Clinical Practice 29, no. 3 (April 2023): 554–64, https://doi.org/10.1111/jep.13789. [xi] Kimmelman and Tannock, “The Paradox of Precision Medicine.” [xii] Vogt and Hofmann, 1206. [xiii] Vogt and Hofmann, 1206. [xiv] Vogt and Hofmann, 1206. [xv] Vogt and Hofmann, 1207. [xvi] Vogt and Hofmann, 1207. [xvii] Vogt and Hofmann, 1207. [xviii] Vogt and Hofmann, 1210. [xix] Mehar Sahu et al., “Chapter Three - Artificial Intelligence and Machine Learning in Precision Medicine: A Paradigm Shift in Big Data Analysis,” in Progress in Molecular Biology and Translational Science, ed. David B. Teplow, vol. 190, 1 vols., Precision Medicine (Academic Press, 2022), 57–100, https://doi.org/10.1016/bs.pmbts.2022.03.002. [xx] Stefan Feuerriegel et al., “Causal Machine Learning for Predicting Treatment Outcomes,” Nature Medicine 30, no. 4 (April 2024): 958–68, https://doi.org/10.1038/s41591-024-02902-1. [xxi] Sunderland Baker et al., “Ethical Considerations in Closed Loop Deep Brain Stimulation,” Deep Brain Stimulation 3 (October 1, 2023): 8–15, https://doi.org/10.1016/j.jdbs.2023.11.001. [xxii] David Haslacher et al., “AI for Brain-Computer Interfaces,” 2024, 7, https://doi.org/10.1016/bs.dnb.2024.02.003. [xxiii] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 103–4; “Premarket Approval (PMA),” https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100026. [xxiv] Burdette and Swartz, “Chapter 4 - Responsive Neurostimulation,” 104. [xxv] Burdette and Swartz, 126. [xxvi] Sean L. Metzger et al., “A High-Performance Neuroprosthesis for Speech Decoding and Avatar Control,” Nature 620, no. 7976 (August 2023): 1037–46, https://doi.org/10.1038/s41586-023-06443-4. [xxvii] Hao Fang and Yuxiao Yang, “Predictive Neuromodulation of Cingulo-Frontal Neural Dynamics in Major Depressive Disorder Using a Brain-Computer Interface System: A Simulation Study,” Frontiers in Computational Neuroscience 17 (March 6, 2023), https://doi.org/10.3389/fncom.2023.1119685; Mahsa Malekmohammadi et al., “Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson’s Disease,” Movement Disorders 31, no. 3 (2016): 426–28, https://doi.org/10.1002/mds.26482. [xxviii] Young-Hoon Nho et al., “Responsive Deep Brain Stimulation Guided by Ventral Striatal Electrophysiology of Obsession Durably Ameliorates Compulsion,” Neuron 0, no. 0 (October 20, 2023), https://doi.org/10.1016/j.neuron.2023.09.034. [xxix] Nho et al. [xxx] Nho et al.; Erik Robinson, “Brain Implant at OHSU Successfully Controls Both Seizures and OCD,” OHSU News, accessed March 3, 2024, https://news.ohsu.edu/2023/10/25/brain-implant-at-ohsu-successfully-controls-both-seizures-and-ocd. [xxxi] Awuah et al., “Bridging Minds and Machines”; Haslacher et al., “AI for Brain-Computer Interfaces.” [xxxii] Awuah et al., “Bridging Minds and Machines.” [xxxiii] Sara Green, Barbara Prainsack, and Maya Sabatello, “The Roots of (in)Equity in Precision Medicine: Gaps in the Discourse,” Personalized Medicine 21, no. 1 (January 2024): 5–9, https://doi.org/10.2217/pme-2023-0097. [xxxiv] Green, Prainsack, and Sabatello, 7. [xxxv] Robyn Bluhm and Kirstin Borgerson, “An Epistemic Argument for Research-Practice Integration in Medicine,” The Journal of Medicine and Philosophy: A Forum for Bioethics and Philosophy of Medicine 43, no. 4 (July 9, 2018): 469–84, https://doi.org/10.1093/jmp/jhy009. [xxxvi] Vijay Mahant, “‘Right-to-Try’ Experimental Drugs: An Overview,” Journal of Translational Medicine 18 (June 23, 2020): 253, https://doi.org/10.1186/s12967-020-02427-4. [xxxvii] Michael S. Okun et al., “Deep Brain Stimulation in the Internal Capsule and Nucleus Accumbens Region: Responses Observed during Active and Sham Programming,” Journal of Neurology, Neurosurgery & Psychiatry 78, no. 3 (March 1, 2007): 310–14, https://doi.org/10.1136/jnnp.2006.095315. (shrink)

Neuropsychiatry integrates neuroscience and clinical pathophysiology of the human brain-mind interface. Kalisch et al. provide an important advance with a clear, quantitative, unified neuropsychiatric model of resilience, a crucial adaptive response to adversity. They highlight positive appraisal style, describing underlying neural circuitry and mechanisms. This provides a foundation for the development of biomarkers and targeted therapeutics across the range of neuropsychiatric disorders.

Background The rise of a new generation of intelligent neuroprostheses, brain-computer interfaces (BCI) and adaptive closed-loop brain stimulation devices hastens the clinical deployment of neurotechnologies to treat neurological and neuropsychiatric disorders. However, it remains unclear how these nascent technologies may impact the subjective experience of their users. To inform this debate, it is crucial to have a solid understanding how more established current technologies already affect their users. In recent years, researchers have used qualitative research methods to explore (...) the subjective experience of individuals who become users of clinical neurotechnology. Yet, a synthesis of these more recent findings focusing on qualitative methods is still lacking. Methods To address this gap in the literature, we systematically searched five databases for original research articles that investigated subjective experiences of persons using or receiving neuroprosthetics, BCIs or neuromodulation with qualitative interviews and raised normative questions. Results 36 research articles were included and analysed using qualitative content analysis. Our findings synthesise the current scientific literature and reveal a pronounced focus on usability and other technical aspects of user experience. In parallel, they highlight a relative neglect of considerations regarding agency, self-perception, personal identity and subjective experience. Conclusions Our synthesis of the existing qualitative literature on clinical neurotechnology highlights the need to expand the current methodological focus as to investigate also non-technical aspects of user experience. Given the critical role considerations of agency, self-perception and personal identity play in assessing the ethical and legal significance of these technologies, our findings reveal a critical gap in the existing literature. This review provides a comprehensive synthesis of the current qualitative research landscape on neurotechnology and the limitations thereof. These findings can inform researchers on how to study the subjective experience of neurotechnology users more holistically and build patient-centred neurotechnology. (shrink)

Advances in neuroscience have revolutionized our understanding of the central nervous system. Neuroimaging technologies, in particular, have begun to reveal the complex anatomical, physiological, biochemical, genetic, and molecular organizational structure of the organ at the center of that system: the human brain. More recently, neuroimaging technologies have enabled the investigation of normal brain function and are being used to gain important new insights into the mechanisms behind many neuropsychiatric disorders. This research has implications for psychiatric diagnosis, treatment, and (...) risk assessment. However, with some exceptions, neuroimaging is still a research tool—not ready for use in clinical psychiatry. (shrink)

The presence of asymmetry in the human cerebral hemispheres is detectable at both the macroscopic and microscopic scales. The horizontal expansion of cortical surface during development (within individual brains), and across evolutionary time (between species), is largely due to the proliferation and spacing of the microscopic vertical columns of cells that form the cortex. In the asymmetric planum temporale (PT), minicolumn width asymmetry is associated with surface area asymmetry. Although the human minicolumn asymmetry is not large, it is estimated to (...) account for a surface area asymmetry of approximately 9% of the region’s size. Critically, this asymmetry of minicolumns is absent in the equivalent areas of the brains of other apes. The left-hemisphere dominance for processing speech is thought to depend, partly, on a bias for higher resolution processing across widely spaced minicolumns with less overlapping dendritic fields, whereas dense minicolumn spacing in the right hemisphere is associated with more overlapping, lower resolution, holistic processing. This concept refines the simple notion that a larger brain area is associated with dominance for a function and offers an alternative explanation associated with “processing type.” This account is mechanistic in the sense that it offers a mechanism whereby asymmetrical components of structure are related to specific functional biases yielding testable predictions, rather than the generalization that “bigger is better” for any given function. Face processing provides a test case – it is the opposite of language, being dominant in the right hemisphere. Consistent with the bias for holistic, configural processing of faces, the minicolumns in the right-hemisphere fusiform gyrus are thinner than in the left hemisphere, which is associated with featural processing. Again, this asymmetry is not found in chimpanzees. The difference between hemispheres may also be seen in terms of processing speed, facilitated by asymmetric myelination of white matter tracts ( Anderson et al., 1999 found that axons of the left posterior superior temporal lobe were more thickly myelinated). By cross-referencing the differences between the active fields of the two hemispheres, via tracts such as the corpus callosum, the relationship of local features to global features may be encoded. The emergent hierarchy of features within features is a recursive structure that may functionally contribute to generativity – the ability to perceive and express layers of structure and their relations to each other. The inference is that recursive generativity, an essential component of language, reflects an interaction between processing biases that may be traceable in the microstructure of the cerebral cortex. Minicolumn organization in the PT and the prefrontal cortex has been found to correlate with cognitive scores in humans. Altered minicolumn organization is also observed in neuropsychiatric disorders including autism and schizophrenia. Indeed, altered interhemispheric connections correlated with minicolumn asymmetry in schizophrenia may relate to language-processing anomalies that occur in the disorder. Schizophrenia is associated with over-interpretation of word meaning at the semantic level and over-interpretation of relevance at the level of pragmatic competence, whereas autism is associated with overly literal interpretation of word meaning and under-interpretation of social relevance at the pragmatic level. Both appear to emerge from a disruption of the ability to interpret layers of meaning and their relations to each other. This may be a consequence of disequilibrium in the processing of local and global features related to disorganization of minicolumnar units of processing. (shrink)

Our sense of self includes awareness of our thoughts and movements, and our control over them. This feeling can be altered or lost in neuropsychiatric disorders as well as in phenomena such as “automatic writing” whereby writing is attributed to an external source. Here, we employed suggestion in highly hypnotically suggestible participants to model various experiences of automatic writing during a sentence completion task. Results showed that the induction of hypnosis, without additional suggestion, was associated with a small (...) but significant reduction of control, ownership, and awareness for writing. Targeted suggestions produced a double dissociation between thought and movement components of writing, for both feelings of control and ownership, and additionally, reduced awareness of writing. Overall, suggestion produced selective alterations in the control, ownership, and awareness of thought and motor components of writing, thus enabling key aspects of automatic writing, observed across different clinical and cultural settings, to be modelled. (shrink)

Gestational factors play a role in the development of several neuropsychiatric disorders including schizophrenia and autism. In utero conditions influence future mental health through epigenetic mechanisms, which alter gene expression without affecting DNA coding sequence. Environmental factors account for at least 60% of the risk for developing major depression, and earlier onset of depressive illness has been observed over the past decades. I speculate that gestational factors may play a greater role in programing depression than previously recognized. Here, (...) I examine recent evidence for a role for gestational factors in programing mood disorders, and how epigenetic mechanisms mediate this effect. (shrink)

Brain structural covariance network can delineate the brain synchronized alterations in a long-range time period. It has been used in the research of cognition or neuropsychiatric disorders. Recently, causal analysis of structural covariance network, winner-take-all and cortex–subcortex covariance network, and modulation analysis of structural covariance network have expended the technology breadth of SCN. However, the lack of user-friendly software limited the further application of SCN for the research. In this work, we developed the graphical user interface toolkit of (...) brain structural covariance connectivity based on MATLAB platform. The software contained the analysis of SCN, CaSCN, MOD-SCN, and WTA-CSSCN. Also, the group comparison and result-showing modules were included in the software. Furthermore, a simple showing of demo dataset was presented in the work. We hope that the toolkit could help the researchers, especially clinical researchers, to do the brain covariance connectivity analysis in further work more easily. (shrink)

This book is a discussion of the most timely and contentious issues in the two branches of neuroethics: the neuroscience of ethics; and the ethics of neuroscience. Drawing upon recent work in psychiatry, neurology, and neurosurgery, it develops a phenomenologically inspired theory of neuroscience to explain the brain-mind relation. The idea that the mind is shaped not just by the brain but also by the body and how the human subject interacts with the environment has significant implications for free will, (...) moral responsibility, and moral justification of actions. It also provides a better understanding of how different interventions in the brain can benefit or harm us. In addition, the book discusses brain imaging techniques to diagnose altered states of consciousness, deep-brain stimulation to treat neuropsychiatric disorders, and restorative neurosurgery for neurodegenerative diseases. It examines the medical and ethical trade-offs of these interventions in the brain when they produce both positive and negative physical and psychological effects, and how these trade-offs shape decisions by physicians and patients about whether to provide and undergo them. (shrink)

Gilles de la Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterised by the presence of motor and vocal tics. Patients with malignant TS experience severe disease sequelae; risking morbidity and mortality due to tics, self-harm, psychiatric comorbidities and suicide. By definition, those cases termed ‘malignant’ are refractory to all conventional psychiatric and pharmacological regimens. In these instances, deep brain stimulation (DBS) may be efficacious. Current 2015 guidelines recommend a 6-month period absent of suicidal ideation before DBS is offered (...) to patients with TS. We therefore wondered whether it may be ethically justifiable to offer DBS to a minor with malignant TS. We begin with a discussion of non-maleficence and beneficence. New evidence suggests that suicide risk in young patients with TS has been underestimated. In turn, DBS may represent an invaluable opportunity for children with malignant TS to secure future safety, independence and fulfilment. Postponing treatment is associated with additional risks. Ultimately, we assert this unique risk-benefit calculus justifies offering DBS to paediatric patients with malignant TS. A multidisciplinary team of clinicians must determine whether DBS is in the best interest of their individual patients. We conclude with a suggestion for future TS-DBS guidelines regarding suicidal ideation. The importance of informed consent and assent is underscored. (shrink)

Neuroimaging techniques have made a huge contribution to our understanding of schizophrenia and other neuropsychiatric disorders. Until now however, texts on both schizophrenia and neuroimaging have paid little attention to the overlap between these areas. This new volume is the first dedicated to unravelling how these techniques can help us better understand this complex disorder. Each chapter focuses on a particular research method, describing the nature of the findings, the main technological problems, and future possibilities. Though including sufficient (...) methodological detail to be of value to imaging researchers, the emphasis throughout is on providing information of value to clinicians. Written and edited by leaders in schizophrenia research, this book details what structural and functional brain imaging studies have already established about schizophrenia and what developments are likely in the foreseeable future. (shrink)

Long-term potentiation is one of the most extensively studied forms of neuroplasticity and is considered the strongest candidate mechanism for memory and learning. The use of event-related potentials and sensory stimulation paradigms has allowed for the translation from animal studies to non-invasive studies of LTP-like synaptic plasticity in humans. Accumulating evidence suggests that synaptic plasticity as measured by stimulus-specific response modulation is reduced in neuropsychiatric disorders such as major depressive disorder, bipolar disorders and schizophrenia, suggesting that impaired (...) synaptic plasticity plays a part in the underlying pathophysiology of these disorders. This is in line with the neuroplasticity hypothesis of depression, which postulate that deficits in neuroplasticity might be a common pathway underlying depressive disorders. The current study aims to replicate and confirm earlier reports that visual stimulus-specific response modulation is a viable probe into LTP-like synaptic plasticity in a large sample of healthy adults. Further, this study explores whether impairments in LTP-like synaptic plasticity is associated with self-reported subclinical depressive symptoms and stress in a healthy population. Consistent with prior research, the current study replicated and confirmed reports demonstrating significant modulation of visual evoked potentials following visual high-frequency stimulation. Current results further indicate that reduced LTP-like synaptic plasticity is associated with higher levels of self-reported symptoms of depression and perceived stress. This indicate that LTP-like plasticity is sensitive to sub-clinical levels of psychological distress, and might represent a vulnerability marker for the development of depressive symptoms. (shrink)

Brain implants, such as Deep Brain Stimulation (DBS), which are designed to improve motor, mood and behavioural pathology, present unique challenges to our understanding of identity, agency and free will. This is because these devices can have visible effects on persons' physical and psychological properties yet are essentially undetectable when operating correctly. They can supplement and compensate for one's inherent abilities and faculties when they are compromised by neuropsychiatric disorders. Further, unlike talk therapy or pharmacological treatments, patients need (...) not ‘do’ anything for the treatment to take effect. If one accepts, as we argue here, that brain implants are unique among implantable types of devices, then this can have significant implications for what it means to persist as the same person and be the source of one's thoughts and actions. By examining two of the most common indications for DBS in current use, namely in the motor (Parkinson's Disease) and psychiatric (Major Depression) domains, we further argue that although DBS, as it is currently applied, does not necessarily represent a unique threat to personal identity and agency per se, it introduces an unprecedented ‘third party’ into the debate on these concepts. In this way, DBS can be used as a tool to begin probing, both conceptually and empirically, some of philosophy's most perennial metaphysical questions. (shrink)

Disruptions in chromatin regulator genes are frequently the cause of neurodevelopmental and neuropsychiatric disorders. Chromatin regulators are widely expressed in the brain, yet symptoms suggest that specific circuits can be preferentially altered when they are mutated. Using Drosophila allows targeted manipulation of chromatin regulators in defined neuronal classes, lineages, or circuits, revealing their roles in neuronal precursor self‐renewal, dendrite and axon targeting, neuron diversification, and the tuning of developmental signaling pathways. Phenotypes arising from chromatin regulator disruption are context (...) dependent – defined by interaction networks between the regulators, transcription factors, and chromatin remodeling complex partners. Future challenges are to determine the complexity of partner interactions, and to ascertain the degree to which cognitive deficits are due to loss of chromatin regulator activity in building a circuit or in maintaining homeostasis and activity within it. (shrink)