John Noel M. Viaña

Illuminating the role of cholinergic signaling in circuits of attention and emotionally salient behaviors.

Acetylcholine (ACh) signaling underlies specific aspects of cognitive functions and behaviors, including attention, learning, memory and motivation. Alterations in ACh signaling are involved in the pathophysiology of multiple neuropsychiatric disorders. In the central nervous system, ACh transmission is mainly guaranteed by dense innervation of select cortical and subcortical regions from disperse groups of cholinergic neurons within the basal forebrain (BF; e.g., diagonal band, medial septal, nucleus basalis) and the pontine-mesencephalic nuclei, respectively. Despite the fundamental role of cholinergic signaling in the CNS and the long standing knowledge of the organization of cholinergic circuitry, remarkably little is known about precisely how ACh release modulates cortical and subcortical neural activity and the behaviors these circuits subserve. Growing interest in cholinergic signaling in the CNS focuses on the mechanism(s) of action by which endogenously released ACh regulates cognitive functions, acting as a neuromodulator and/or as a direct transmitter via nicotinic and muscarinic receptors. The development of optogenetic techniques has provided a valuable toolbox with which we can address these questions, as it allows the selective manipulation of the excitability of cholinergic inputs to the diverse array of cholinergic target fields within cortical and subcortical domains. Here, we review recent papers that use the light-sensitive opsins in the cholinergic system to elucidate the role of ACh in circuits related to attention and emotionally salient behaviors. In particular, we highlight recent optogenetic studies which have tried to disentangle the precise role of ACh in the modulation of cortical-, hippocampal- and striatal-dependent functions.

Ethical considerations for deep brain stimulation trials in patients with early-onset Alzheimer’s disease

Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimers disease, with several recruiting participants <65 and thus have early-onset Alzheimers disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

Beyond genomic association: ethical implications of elucidating disease mechanisms and genotype-influenced treatment response

Beyond Genomic Association: Ethical Implications of Elucidating Disease Mechanisms and GenotypeInfluenced Treatment Response John Noel M. Viaña, Roemel Jeusep Bueno & Frederic Gilbert To cite this article: John Noel M. Viaña, Roemel Jeusep Bueno & Frederic Gilbert (2017) Beyond Genomic Association: Ethical Implications of Elucidating Disease Mechanisms and Genotype-Influenced Treatment Response, The American Journal of Bioethics, 17:4, 24-26, DOI: 10.1080/15265161.2017.1284931 To link to this article: http://dx.doi.org/10.1080/15265161.2017.1284931

Deep brain stimulation for people with Alzheimer’s disease: Anticipating potential effects on the tripartite self

Memory dysfunction and cognitive impairments due to Alzheimer’s disease can affect the selfhood and identity of afflicted individuals, causing distress to both people with Alzheimer’s disease and their caregivers. Recently, a number of case studies and clinical trials have been conducted to determine the potential of deep brain stimulation as a therapeutic modality for people with Alzheimer’s disease. Some of these studies have shown that deep brain stimulation could induce flashbacks and stabilize or even improve memory. However, deep brain stimulation itself has also been attributed as a potential threat to identity and selfhood, especially when procedure-related adverse events arise. We anticipate potential effects of deep brain stimulation for people with Alzheimer’s disease on selfhood, reconciling information from medical reports, psychological, and sociological investigations on the impacts of deep brain stimulation or Alzheimer’s disease on selfhood. A tripartite model of the self that extends the scope of Rom Harré’s and Steve Sabat’s social constructionist framework was used. In this model, potential effects of deep brain stimulation for Alzheimer’s disease on Self 1 or singularity through use of first-person indexicals, and gestures of self-reference, attribution, and recognition; Self 2 or past and present attributes, knowledge of these characteristics, and continuity of narrative identity; and Self 3 or the relational and social self are explored. The ethical implications of potential effects of deep brain stimulation for Alzheimer’s disease on the tripartite self are then highlighted, focusing on adapting informed consent procedures and care provided throughout the trial to account for both positive and negative plausible effects on Self 1, Self 2, and Self 3.

Acquired Pedophilia and Moral Responsibility

have access only to rationally egoistic reasons and they can be claimed not to possess something essential for moral behavior (the impartial observer standpoint); in this way, moral responsibility may be undermined. Finally, the question for discussion I would like to pose is whether the proposed model has the potential to be broadly applied to all significant wrongdoing, including persons who do not carry a neuropsychiatric diagnosis. Subclinical deficits in relevant capacities may be much more prevalent, and I am inclined to think that even if this model is a first-step approach, for the conceptual framework the answer should be in the affirmative. Deficits in neuropsychological testing of the relevant capacities and/or defects in reasoning (reason recognition, weighing, and response), and/or structural and functional alterations leading to fMRI evidence of reduced connectivity of relevant neuronal networks, should all potentially offer a discount to attributions of responsibility and blameworthiness. Concurrently, we should be thinking about whether these deficits are remediable, starting with approaches such as morality and rationality training to more sophisticated, invasive, futuristic and controversial approaches such as artificial moral enhancement via manipulation of functional connectivity.& REFERENCES

Enthusiastic portrayal of 3D bioprinting in the media: Ethical side effects

There has been a surge in mass media reports extolling the potential for using three-dimensional printing of biomaterials (3D bioprinting) to treat a wide range of clinical conditions. Given that mass media is recognized as one of the most important sources of health and medical information for the general public, especially prospective patients, we report and discuss the ethical consequences of coverage of 3D bioprinting in the media. First, we illustrate how positive mass media narratives of a similar biofabricated technology, namely the Macchiarini scaffold tracheas, which was involved in lethal experimental human trials, influenced potential patient perceptions. Second, we report and analyze the positively biased and enthusiastic portrayal of 3D bioprinting in mass media. Third, we examine the lack of regulation and absence of discussion about risks associated with bioprinting technology. Fourth, we explore how media misunderstanding is dangerously misleading the narrative about the technology.

Of Meatballs And Invasive Neurotechnological Trials: Additional Considerations for Complex Clinical Decisions

Using this case, Lavazza and Reichlin (2018) explored the ethical dilemmas associated with decision making in people with Alzheimer’s disease (AD), specifically when their new preferences conflict ...

Big Explanations for Big Expectations: Deriving Lessons From the Human Genome and Blue Brain Projects

With a budget of almost a billion euros (Marquardt 2015), the Human Brain Project (HBP) is one of the biggest biology projects that humanity has undertaken, just trailing behind the Human Genome Pr...

Decoded neurofeedback: eligibility, applicability, and reliability issues for use in schizophrenia and major depressive disorder

Recent progress in neuroimaging has paved the way for modalities that allow elucidation not only of brain structure but also of brain function. Among these developments is functional magnetic resonance imaging (fMRI), a noninvasive, high-spatial-resolution method that records bloodoxygenation-level-dependent signals in the brain to track hemodynamic responses that indirectly measure brain activity (Fovet, Jardri, and Linden 2015). Further technological advancements in fMRI then allowed analysis and display of functional information in real time, expanding fMRI’s capabilities in clinical diagnosis and opening up its potential for use as treatment via real-time fMRI neurofeedback (rtfMRI-NF). In rtfMRI-NF, patients use representations of real-time reported brain activity patterns to facilitate learned self-regulation with the goal of changing behavior, cognition, or brain function (Stoeckel et al. 2014). This has been taken a step further with the introduction of decoded neurofeedback (Shibata et al. 2011), which applies a multivariate analysis to real-time fMRI feedback (Esmail and Linden 2011), expanding its spatial specificity and selection flexibility and allowing for an approach that is not a priori in defining neural networks of interest (Esmail and Linden 2011). Ultimately, real-time fMRI decoded neurofeedback (dNF) could bring potential new treatments for mental disorders.