Searching for information about stem cells online in an age of artificial intelligence: How should the stem cell community respond?

Patients and their families routinely use the Internet to learn about stem cell research. What they find, is increasingly influenced by ongoing changes in how information is filtered and presented online. This article reflects on recent developments in generative artificial intelligence and how the stem cell community should respond.

Environmentality in biomedicine: microbiome research and the perspectival body.

Microbiome research shows that human health is foundationally intertwined with the ecology of microbial communities living on and in our bodies. This challenges the categorical separation of organisms from environments that has been central to biomedicine, and questions the boundaries between them. Biomedicine is left with an empirical problem: how to understand causal pathways between host health, microbiota and environment? We propose a conceptual tool - environmentality - to think through this problem. Environmentality is the state or quality of being an environment for something else in a particular context: a fully perspectival proposition. Its power lies partly in what Isabelle Stengers has called the efficacy of the word itself, contrasting the dominant sense of the word environment as something both external and fixed. Through three case studies, we argue that environmentality can help think about the causality of microbiota vis-a-vis host health in a processual, relational and situated manner, across scales and temporalities. We situate this intervention within historical trajectories of thought in biomedicine, focusing on the challenge microbiome research poses to an aperspectival body. We argue that addressing entanglements between microbial and human lives requires that the environment is brought into the clinic, thus shortening the conceptual gap between medicine and public health.

Mind the Gut-displaying microbiome research through artistic collaboration.

This paper presents the Mind the Gut exhibition, opened in 2017 at the Medical Museion, the University of Copenhagen's museum for the culture and history of medicine. It is an experimental exhibition combining science, art, and history in an examination of the relationship between mind and gut, including the trillions of microbes that inhabits them. Mind the Gut was the result of a 2-year-long research and curatorial process, which began in 2015 when Museion was awarded the Bikuben Foundation Vision Award. The exhibition brings together the long history of attempts to understand and intervene in the relationship between mind and gut, between emotions and digestion with cutting-edge biomedical research, and includes the perspectives of science, medicine, and personal experience, via a combination of artworks, historical objects from the Medical Museion collections, items from laboratories, and individual stories. The exhibition is organized around different ways the body has been handled in order to intervene in interactions between mind, gut, and bacteria, including imaging, electrifying, feeding, drugging, and opening surgically. This paper outlines some of the thoughts on science communication that motivated the exhibition, discussing why the displays emphasize the exploratory over the explanatory. Also discussed are several artistic collaborations that formed part of the displays. Ultimately, Mind the Gut is created to be a public space that encourages reflection and curiosity, by showing how biomedicine fits into social, cultural, historical, and directly personal contexts. The exhibition does not aim to provide answers about what food the visitors should eat or what the truth of how gut and brain interactions might be. Rather, it emphasizes process over result, hopefully encouraging the visitors to ask their own questions of the relationship between mind and gut, between body and microbes.

Endogenous GABA controls oligodendrocyte lineage cell number, myelination, and CNS internode length.

Adjusting the thickness and internodal length of the myelin sheath is a mechanism for tuning the conduction velocity of axons to match computational needs. Interactions between oligodendrocyte precursor cells (OPCs) and developing axons regulate the formation of myelin around axons. We now show, using organotypic cerebral cortex slices from mice expressing eGFP in Sox10-positive oligodendrocytes, that endogenously released GABA, acting on GABAA receptors, greatly reduces the number of oligodendrocyte lineage cells. The decrease in oligodendrocyte number correlates with a reduction in the amount of myelination but also an increase in internode length, a parameter previously thought to be set by the axon diameter or to be a property intrinsic to oligodendrocytes. Importantly, while TTX block of neuronal activity had no effect on oligodendrocyte lineage cell number when applied alone, it was able to completely abolish the effect of blocking GABAA receptors, suggesting that control of myelination by endogenous GABA may require a permissive factor to be released from axons. In contrast, block of AMPA/KA receptors had no effect on oligodendrocyte lineage cell number or myelination. These results imply that, during development, GABA can act as a local environmental cue to control myelination and thus influence the conduction velocity of action potentials within the CNS. GLIA 2017;65:309-321.

Utilizing social media to study information-seeking and ethical issues in gene therapy.

BACKGROUND: The field of gene therapy is rapidly evolving, and while hopes of treating disorders of the central nervous system and ethical concerns have been articulated within the academic community, little is known about views and opinions of different stakeholder groups. OBJECTIVE: To address this gap, we utilized social media to investigate the kind of information public users are seeking about gene therapy and the hopes, concerns, and attitudes they express. METHODS: We conducted a content analysis of questions containing the keywords "gene therapy" from the Q&A site "Yahoo! Answers" for the 5-year period between 2006 and 2010. From the pool of questions retrieved (N=903), we identified those containing at least one theme related to ethics, environment, economics, law, or society (n=173) and then characterized the content of relevant answers (n=399) through emergent coding. RESULTS: The results show that users seek a wide range of information regarding gene therapy, with requests for scientific information and ethical issues at the forefront of enquiry. The question sample reveals high expectations for gene therapy that range from cures for genetic and nongenetic diseases to pre- and postnatal enhancement of physiological attributes. Ethics questions are commonly expressed as fears about the impact of gene therapy on self and society. The answer sample echoes these concerns but further suggests that the acceptability of gene therapy varies depending on the specific application. CONCLUSIONS: Overall, the findings highlight the powerful role of social media as a rich resource for research into attitudes toward biomedicine and as a platform for knowledge exchange and public engagement for topics relating to health and disease.

Neurobiological narratives: experiences of mood disorder through the lens of neuroimaging.

Many scientists, healthcare providers, policymakers and patients are awaiting in anticipation the application of biomedical technologies such as functional neuroimaging for the prediction, diagnosis and treatment of mental disorders. The potential efficacy of such applications is controversial, and functional neuroimaging is not yet routinely used in psychiatric clinics. However, commercial ventures and enthusiastic reporting indicate a pressing need to engage with the social and ethical issues raised by clinical translation. There has been little investigation of how individuals living with mental illness view functional neuroimaging, or of the potential psychological impacts of its clinical use. We conducted 12 semi-structured interviews with adults diagnosed with major depression or bipolar disorder, probing their experiences with mental health care and their perspectives on the prospect of receiving neuroimaging for prediction, diagnosis and planning treatment. The participants discussed the potential role of neuroimages in (i) mitigating stigma; (ii) supporting morally loaded explanations of mental illness due to an imbalance of brain chemistry; (iii) legitimising psychiatric symptoms, which may have previously been de-legitimised since they lacked objective representation, through objective representations of disorder; and (iv) reifying DSM-IV-TR disorder categories and links to identity. We discuss these anticipated outcomes in the context of participant lived experience and attitudes to biologisation of mental illness, and argue for bringing these voices into upstream ethics discussion.

Treatments for neurodevelopmental disorders: evidence, advocacy, and the Internet.

The Internet is a major source of health-related information for parents of sick children despite concerns surrounding quality. For neurodevelopmental disorders, the websites of advocacy groups are a largely unexamined source of information. We evaluated treatment information posted on nine highly-trafficked advocacy websites for autism, cerebral palsy, and fetal alcohol spectrum disorder. We found that the majority of claims about treatment safety and efficacy were unsubstantiated. Instead, a range of rhetorical strategies were used to imply scientific support. When peer-reviewed publications were cited, 20 % were incorrect or irrelevant. We call for new partnerships between advocacy and experts in developmental disorders to ensure better accuracy and higher transparency about how treatment information is selected and evidenced on advocacy websites.

Attention in a bayesian framework.

The behavioral phenomena of sensory attention are thought to reflect the allocation of a limited processing resource, but there is little consensus on the nature of the resource or why it should be limited. Here we argue that a fundamental bottleneck emerges naturally within Bayesian models of perception, and use this observation to frame a new computational account of the need for, and action of, attention - unifying diverse attentional phenomena in a way that goes beyond previous inferential, probabilistic and Bayesian models. Attentional effects are most evident in cluttered environments, and include both selective phenomena, where attention is invoked by cues that point to particular stimuli, and integrative phenomena, where attention is invoked dynamically by endogenous processing. However, most previous Bayesian accounts of attention have focused on describing relatively simple experimental settings, where cues shape expectations about a small number of upcoming stimuli and thus convey "prior" information about clearly defined objects. While operationally consistent with the experiments it seeks to describe, this view of attention as prior seems to miss many essential elements of both its selective and integrative roles, and thus cannot be easily extended to complex environments. We suggest that the resource bottleneck stems from the computational intractability of exact perceptual inference in complex settings, and that attention reflects an evolved mechanism for approximate inference which can be shaped to refine the local accuracy of perception. We show that this approach extends the simple picture of attention as prior, so as to provide a unified and computationally driven account of both selective and integrative attentional phenomena.

Neuroethics and fMRI: mapping a fledgling relationship.

Human functional magnetic resonance imaging (fMRI) informs the understanding of the neural basis of mental function and is a key domain of ethical enquiry. It raises questions about the practice and implications of research, and reflexively informs ethics through the empirical investigation of moral judgments. It is at the centre of debate surrounding the importance of neuroscience findings for concepts such as personhood and free will, and the extent of their practical consequences. Here, we map the landscape of fMRI and neuroethics, using citation analysis to uncover salient topics. We find that this landscape is sparsely populated: despite previous calls for debate, there are few articles that discuss both fMRI and ethical, legal, or social implications (ELSI), and even fewer direct citations between the two literatures. Recognizing that practical barriers exist to integrating ELSI discussion into the research literature, we argue nonetheless that the ethical challenges of fMRI, and controversy over its conceptual and practical implications, make this essential.

Spatially distributed encoding of covert attentional shifts in human thalamus.

Spatial attention modulates signal processing within visual nuclei of the thalamus--but do other nuclei govern the locus of attention in top-down mode? We examined functional MRI (fMRI) data from three subjects performing a task requiring covert attention to 1 of 16 positions in a circular array. Target position was cued after stimulus offset, requiring subjects to perform target detection from iconic visual memory. We found positionally specific responses at multiple thalamic sites, with individual voxels activating at more than one direction of attentional shift. Voxel clusters at anatomically equivalent sites across subjects revealed a broad range of directional tuning at each site, with little sign of contralateral bias. By reference to a thalamic atlas, we identified the nuclear correspondence of the four most reliably activated sites across subjects: mediodorsal/central-intralaminar (oculomotor thalamus), caudal intralaminar/parafascicular, suprageniculate/limitans, and medial pulvinar/lateral posterior. Hence, the cortical network generating a top-down control signal for relocating attention acts in concert with a spatially selective thalamic apparatus-the set of active nuclei mirroring the thalamic territory of cortical "eye-field" areas, thus supporting theories which propose the visuomotor origins of covert attentional selection.

Effects of category-specific costs on neural systems for perceptual decision-making.

Perceptual judgments are often biased by prospective losses, leading to changes in decision criteria. Little is known about how and where sensory evidence and cost information interact in the brain to influence perceptual categorization. Here we show that prospective losses systematically bias the perception of noisy face-house images. Asymmetries in category-specific cost were associated with enhanced blood-oxygen-level-dependent signal in a frontoparietal network. We observed selective activation of parahippocampal gyrus for changes in category-specific cost in keeping with the hypothesis that loss functions enact a particular task set that is communicated to visual regions. Across subjects, greater shifts in decision criteria were associated with greater activation of the anterior cingulate cortex (ACC). Our results support a hypothesis that costs bias an intermediate representation between perception and action, expressed via general effects on frontal cortex, and selective effects on extrastriate cortex. These findings indicate that asymmetric costs may affect a neural implementation of perceptual decision making in a similar manner to changes in category expectation, constituting a step toward accounting for how prospective losses are flexibly integrated with sensory evidence in the brain.

Implicit knowledge of visual uncertainty guides decisions with asymmetric outcomes.

Perception is an "inverse problem," in which the state of the world must be inferred from the sensory neural activity that results. However, this inference is both ill-posed (Helmholtz, 1856; Marr, 1982) and corrupted by noise (Green & Swets, 1989), requiring the brain to compute perceptual beliefs under conditions of uncertainty. Here we show that human observers performing a simple visual choice task under an externally imposed loss function approach the optimal strategy, as defined by Bayesian probability and decision theory (Berger, 1985; Cox, 1961). In concert with earlier work, this suggests that observers possess a model of their internal uncertainty and can utilize this model in the neural computations that underlie their behavior (Knill & Pouget, 2004). In our experiment, optimal behavior requires that observers integrate the loss function with an estimate of their internal uncertainty rather than simply requiring that they use a modal estimate of the uncertain stimulus. Crucially, they approach optimal behavior even when denied the opportunity to learn adaptive decision strategies based on immediate feedback. Our data thus support the idea that flexible representations of uncertainty are pre-existing, widespread, and can be propagated to decision-making areas of the brain.

Visual processing and the bodily self.

The 'body schema' has traditionally been defined as a passively updated, proprioceptive representation of the body. However, recent work has suggested that body representations are more complex and flexible than previously thought. They may integrate current perceptual information from all sensory modalities, and can be extended to incorporate indirect representations of the body and functional portions of tools. In the present study, we investigate the source of a facilitatory effect of viewing the body on speeded visual discrimination reaction times. Participants responded to identical visual stimuli that varied only in their context: being presented on the participant's own body, on the experimenter's body, or in a neutral context. The stimuli were filmed and viewed in real-time on a projector screen. Careful controls for attention, biological saliency, and attribution confirmed that the facilitatory effect depends critically on participants attributing the context to a real body. An intermediate effect was observed when the stimuli were presented on another person's body, suggesting that the effect of viewing one's own body might represent a conjunction of an interpersonal body effect and an egocentric effect.

Spatial consequences of bridging the saccadic gap.

We report six experiments suggesting that conscious perception is actively redrafted to take account of events both before and after the event that is reported. When observers saccade to a stationary object they overestimate its duration, as if the brain were filling in the saccadic gap with the post-saccadic image. We first demonstrate that this illusion holds for moving objects, implying that the perception of time, velocity, and distance traveled become discrepant. We then show that this discrepancy is partially resolved up to 500 ms after a saccade: the perceived offset position of a post-saccadic moving stimulus shows a greater forward mislocalization when pursued after a saccade than during pursuit alone. These data are consistent with the idea that the temporal bias is resolved by the subsequent spatial adjustment to provide a percept that is coherent in its gist but inconsistent in its detail.

Biases in the perceived timing of perisaccadic perceptual and motor events.

Subjects typically experience the temporal interval immediately following a saccade as longer than a comparable control interval. One explanation of this effect is that the brain antedates the perceptual onset of a saccade target to around the time of saccade initiation. This could explain the apparent continuity of visual perception across eye movements. This antedating account was tested in three experiments in which subjects made saccades of differing extents and then judged either the duration or the temporal order of key events. Postsaccadic stimuli underwent subjective temporal lengthening and had early perceived onsets. A temporally advanced awareness of saccade completion was also found, independently of antedating effects. These results provide convergent evidence supporting antedating and differentiating it from other temporal biases.

Facilitated processing of visual stimuli associated with the body.

Recent work on tactile perception has revealed enhanced tactile acuity and speeded spatial-choice reaction times (RTs) when viewing the stimulated body site as opposed to viewing a neutral object. Here we examine whether this body-view enhancement effect extends to visual targets. Participants performed a speeded spatial discrimination between two lights attached either to their own left index finger or to a wooden finger-shaped object, making a simple distal--proximal decision. We filmed either the finger-mounted or the object-mounted lights in separate experimental blocks and the live scene was projected onto a screen in front of the participants. Thus, participants responded to identical visual targets varying only in their context: on the body or not. Results revealed a large performance advantage for the finger-mounted stimuli: reaction times were substantially reduced, while discrimination accuracy was unaffected. With this finding we address concerns associated with previous work on the processing of stimuli attributed to the self and extend the finding of a performance advantage for such stimuli to vision.