Brain organoids, consciousness, ethics and moral status.

Advances in the field of human stem cells are often a source of public and ethical controversy. Researchers must frequently balance diverse societal perspectives on questions of morality with the pursuit of medical therapeutics and innovation. Recent developments in brain organoids make this challenge even more acute. Brain organoids are a new class of brain surrogate generated from human pluripotent stem cells (hPSCs). They have gained traction as a model for studying the intricacies of the human brain by using advancements in stem cell biology to recapitulate aspects of the developing human brain in vitro. However, recent observation of neural oscillations spontaneously emerging from these organoids raises the question of whether brain organoids are or could become conscious. At the same time, brain organoids offer a potentially unique opportunity to scientifically understand consciousness. To address these issues, experimental biologists, philosophers, and ethicists united to discuss the possibility of consciousness in human brain organoids and the consequent ethical and moral implications.

Dynamics of neural recruitment surrounding the spontaneous arising of thoughts in experienced mindfulness practitioners.

Thoughts arise spontaneously in our minds with remarkable frequency, but tracking the brain systems associated with the early inception of a thought has proved challenging. Here we addressed this issue by taking advantage of the heightened introspective ability of experienced mindfulness practitioners to observe the onset of their spontaneously arising thoughts. We found subtle differences in timing among the many regions typically recruited by spontaneous thought. In some of these regions, fMRI signal peaked prior to the spontaneous arising of a thought - most notably in the medial temporal lobe and inferior parietal lobule. In contrast, activation in the medial prefrontal, temporopolar, mid-insular, lateral prefrontal, and dorsal anterior cingulate cortices peaked together with or immediately following the arising of spontaneous thought. We propose that brain regions that show antecedent recruitment may be preferentially involved in the initial inception of spontaneous thoughts, while those that show later recruitment may be preferentially involved in the subsequent elaboration and metacognitive processing of spontaneous thoughts. Our findings highlight the temporal dynamics of neural recruitment surrounding the emergence of spontaneous thoughts and may help account for some of spontaneous thought's peculiar qualities, including its wild diversity of content and its links to memory and attention.

The Orientations of Large Aspect-Ratio Coiled-Coil Proteins Attached to Gold Nanostructures.

Methods for patterning biomolecules on a substrate at the single molecule level have been studied as a route to sensors with single-molecular sensitivity or as a way to probe biological phenomena at the single-molecule level. However, the arrangement and orientation of single biomolecules on substrates has been less investigated. Here, the arrangement and orientation of two rod-like coiled-coil proteins, cortexillin and tropomyosin, around patterned gold nanostructures is examined. The high aspect ratio of the coiled coils makes it possible to study their orientations and to pursue a strategy of protein orientation via two-point attachment. The proteins are anchored to the surfaces using thiol groups, and the number of cysteine residues in tropomyosin is varied to test how this variation affects the structure and arrangement of the surface-attached proteins. Molecular dynamics studies are used to interpret the observed positional distributions. Based on initial studies of protein attachment to gold post structures, two 31-nm-long tropomyosin molecules are aligned between the two sidewalls of a trench with a width of 68 nm. Because the approach presented in this study uses one of twenty natural amino acids, this method provides a convenient way to pattern biomolecules on substrates using standard chemistry.

Strengthening emotion-cognition integration.

Pessoa's (2013) integrative model of emotion and cognition can be strengthened in two ways: first, by clarification and refinement of key concepts and terminology, and second by the incorporation of an additional key neural system into the model, the locus coeruleus/norepinephrine system.

Traditional Plant-Derived Compounds Inhibit Cell Migration and Induce Novel Cytoskeletal Effects in Glioblastoma Cells.

Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumour recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumour dissemination and regrowth. One current aim of GBM research focuses on assessing the anti-migratory properties of novel or repurposed inhibitors, including plant-based drugs which display anti-cancer properties. We investigated the potential anti-migratory activity of plant-based products with known cytotoxic effects in cancers, using a range of two-dimensional (2D) and three-dimensional (3D) migration and invasion assays as well as immunofluorescence microscopy to determine the specific anti-migratory and phenotypic effects of three plant-derived compounds, Turmeric, Indigo and Magnolia bark, on established glioma cell lines. Migrastatic activity was observed in all three drugs, with Turmeric exerting the most inhibitory effect on GBM cell migration into scratches and from the spheroid edge at all the timepoints investigated (p < 0.001). We also observed novel cytoskeletal phenotypes affecting actin and the focal adhesion dynamics. As our in vitro results determined that Turmeric, Indigo and Magnolia are promising migrastatic drugs, we suggest additional experimentation at the whole organism level to further validate these novel findings.

Real-time fMRI links subjective experience with brain activity during focused attention.

Recent advances in brain imaging have improved the measure of neural processes related to perceptual, cognitive and affective functions, yet the relation between brain activity and subjective experience remains poorly characterized. In part, it is a challenge to obtain reliable accounts of participant's experience in such studies. Here we addressed this limitation by utilizing experienced meditators who are expert in introspection. We tested a novel method to link objective and subjective data, using real-time fMRI (rt-fMRI) to provide participants with feedback of their own brain activity during an ongoing task. We provided real-time feedback during a focused attention task from the posterior cingulate cortex, a hub of the default mode network shown to be activated during mind-wandering and deactivated during meditation. In a first experiment, both meditators and non-meditators reported significant correspondence between the feedback graph and their subjective experience of focused attention and mind-wandering. When instructed to volitionally decrease the feedback graph, meditators, but not non-meditators, showed significant deactivation of the posterior cingulate cortex. We were able to replicate these results in a separate group of meditators using a novel step-wise rt-fMRI discovery protocol in which participants were not provided with prior knowledge of the expected relationship between their experience and the feedback graph (i.e., focused attention versus mind-wandering). These findings support the feasibility of using rt-fMRI to link objective measures of brain activity with reports of ongoing subjective experience in cognitive neuroscience research, and demonstrate the generalization of expertise in introspective awareness to novel contexts.

How the human brain goes virtual: distinct cortical regions of the person-processing network are involved in self-identification with virtual agents.

Millions of people worldwide engage in online role-playing with their avatar, a virtual agent that represents the self. Previous behavioral studies have indicated that many gamers identify more strongly with their avatar than with their biological self. Through their avatar, gamers develop social networks and learn new social-cognitive skills. The cognitive neurosciences have yet to identify the neural processes that underlie self-identification with these virtual agents. We applied functional neuroimaging to 22 long-term online gamers and 21 nongaming controls, while they rated personality traits of self, avatar, and familiar others. Strikingly, neuroimaging data revealed greater avatar-referential cortical activity in the left inferior parietal lobe, a region associated with self-identification from a third-person perspective. The magnitude of this brain activity correlated positively with the propensity to incorporate external body enhancements into one's bodily identity. Avatar-referencing furthermore recruited greater activity in the rostral anterior cingulate gyrus, suggesting relatively greater emotional self-involvement with one's avatar. Post-scanning behavioral data revealed superior recognition memory for avatar relative to others. Interestingly, memory for avatar positively covaried with play duration. These findings significantly advance our knowledge about the brain's plasticity to self-identify with virtual agents and the human cognitive-affective potential to live and learn in virtual worlds.

Qigong Training Positively Impacts Both Posture and Mood in Breast Cancer Survivors With Persistent Post-surgical Pain: Support for an Embodied Cognition Paradigm.

Theories of embodied cognition hypothesize interdependencies between psychological well-being and physical posture. The purpose of this study was to assess the feasibility of objectively measuring posture, and to explore the relationship between posture and affect and other patient centered outcomes in breast cancer survivors (BCS) with persistent postsurgical pain (PPSP) over a 12-week course of therapeutic Qigong mind-body training. Twenty-one BCS with PPSP attended group Qigong training. Clinical outcomes were pain, fatigue, self-esteem, anxiety, depression, stress and exercise self-efficacy. Posture outcomes were vertical spine and vertical head angles in the sagittal plane, measured with a 3D motion capture system in three conditions: eyes open (EO), eyes open relaxed (EOR) and eyes closed (EC). Assessments were made before and after the Qigong training. The association between categorical variables (angle and mood) was measured by Cramer's V. In the EO condition, most participants who improved in fatigue and anxiety scales also had better vertical head values. For the EOR condition, a moderate correlation was observed between changes in vertical head angle and changes in fatigue scale. In the EC condition, most of the participants who improved in measures of fatigue also improved vertical head angle. Additionally, pain severity decreased while vertical spine angle improved. These preliminary findings support that emotion and other patient centered outcomes should be considered within an embodied framework, and that Qigong may be a promising intervention for addressing biopsychosocially complex interventions such as PPSP in BCSs.

Affect-biased attention and predictive processing.

In this paper we argue that predictive processing (PP) theory cannot account for the phenomenon of affect-biased attention - prioritized attention to stimuli that are affectively salient because of their associations with reward or punishment. Specifically, the PP hypothesis that selective attention can be analyzed in terms of the optimization of precision expectations cannot accommodate affect-biased attention; affectively salient stimuli can capture our attention even when precision expectations are low. We review the prospects of three recent attempts to accommodate affect with tools internal to PP theory: Miller and Clark's (2018) embodied inference; Seth's (2013) interoceptive inference; and Joffily and Coricelli's (2013) rate of change of free energy. In each case we argue that the account does not resolve the challenge from affect-biased attention. For this reason, we conclude that prediction error minimization is not sufficient to explain all mental phenomena, contrary to the claim that the PP framework provides a unified theory of all mental phenomena or the brain's cognitive functioning. Nevertheless, we suggest that empirical investigation of the interaction between affective salience and precision expectations should prove helpful in understanding the limits of PP theory, and may provide new directions for the application of a Bayesian perspective to perception.

Mindful meta-awareness: sustained and non-propositional.

Meta-awareness appears to be essential to nearly all forms of mindfulness practice, and it plays a key role in processes that are central to therapeutic effects of mindfulness training, including decentering - shifting one's experiential perspective onto an experience itself - and dereification or metacognitive insight - experiencing thoughts as mental events, and not as the things that they seem to represent. Important advances in the conceptualization of meta-awareness in mindfulness have recently been made, yet more clarity is required in order to characterize the type of meta-awareness implicated in the ongoing monitoring of attention and affect, even while attention itself is focused on an explicit object of awareness such as the breath. To enhance research on this form of meta-awareness cultivated in at least some styles of mindfulness, a construct of sustained, non-propositional meta-awareness is proposed.

Co-inhibitory T cell receptor KLRG1: human cancer expression and efficacy of neutralization in murine cancer models.

BACKGROUND: KLRG1 is a lymphocyte co-inhibitory, or immune checkpoint, receptor expressed predominantly on late-differentiated effector and effector memory CD8+ T and NK cells. Targeting of KLRG1 neutralization in murine cancer models has not previously been reported. METHODS: We studied KLRG1 expression in human blood and tumor samples from available genomic datasets. Anti-KLRG1 neutralizing antibody was studied in the murine 4T1 breast cancer as monotherapy, and in the MC38 colon cancer and B16F10 melanoma models as combination therapy with anti-PD-1 antibody. RESULTS: In human blood and tumor samples, KLRG1 expression is aligned with cytotoxic T and NK cell differentiation, and upregulated in human tumor samples after a variety of therapies, potentially contributing to adaptive resistance. In in vivo murine models, anti-KLRG1 antibody monotherapy in the 4T1 breast cancer model reduced lung metastases (decreased lung weights p=0.04; decreased nodule count p=0.002), while anti-KLRG1 + anti-PD-1 combination therapy in the MC38 colon cancer and B16F10 melanoma models produced synergistic benefit greater than anti-PD-1 alone for tumor volume (MC38 p=0.01; B16F10 p=0.007) and survival (MC38 p=0.02; B16F10 p=0.002). CONCLUSIONS: These studies provide the first evidence that inhibition of the KLRG1 pathway enhances immune control of cancer in murine models, and provide target validation for KLRG1 targeting of human cancer. The mechanism of efficacy of KLRG1 blockade in murine models remains to be determined.

Can Tai Chi and Qigong Postures Shape Our Mood? Toward an Embodied Cognition Framework for Mind-Body Research.

Dynamic and static body postures are a defining characteristic of mind-body practices such as Tai Chi and Qigong (TCQ). A growing body of evidence supports the hypothesis that TCQ may be beneficial for psychological health, including management and prevention of depression and anxiety. Although a variety of causal factors have been identified as potential mediators of such health benefits, physical posture, despite its visible prominence, has been largely overlooked. We hypothesize that body posture while standing and/or moving may be a key therapeutic element mediating the influence of TCQ on psychological health. In the present paper, we summarize existing experimental and observational evidence that suggests a bi-directional relationship between body posture and mental states. Drawing from embodied cognitive science, we provide a theoretical framework for further investigation into this interrelationship. We discuss the challenges involved in such an investigation and propose suggestions for future studies. Despite theoretical and practical challenges, we propose that the role of posture in mind-body exercises such as TCQ should be considered in future research.

Affective neuroscience of self-generated thought.

Despite increasing scientific interest in self-generated thought-mental content largely independent of the immediate environment-there has yet to be any comprehensive synthesis of the subjective experience and neural correlates of affect in these forms of thinking. Here, we aim to develop an integrated affective neuroscience encompassing many forms of self-generated thought-normal and pathological, moderate and excessive, in waking and in sleep. In synthesizing existing literature on this topic, we reveal consistent findings pertaining to the prevalence, valence, and variability of emotion in self-generated thought, and highlight how these factors might interact with self-generated thought to influence general well-being. We integrate these psychological findings with recent neuroimaging research, bringing attention to the neural correlates of affect in self-generated thought. We show that affect in self-generated thought is prevalent, positively biased, highly variable (both within and across individuals), and consistently recruits many brain areas implicated in emotional processing, including the orbitofrontal cortex, amygdala, insula, and medial prefrontal cortex. Many factors modulate these typical psychological and neural patterns, however; the emerging affective neuroscience of self-generated thought must endeavor to link brain function and subjective experience in both everyday self-generated thought as well as its dysfunctions in mental illness.

Does Consciousness Disappear in Dreamless Sleep?

Consciousness is often said to disappear in deep, dreamless sleep. We argue that this assumption is oversimplified. Unless dreamless sleep is defined as unconscious from the outset there are good empirical and theoretical reasons for saying that a range of different types of sleep experience, some of which are distinct from dreaming, can occur in all stages of sleep. We introduce a novel taxonomy for describing different kinds of dreamless sleep experiences and suggest research methods for their investigation. Future studies should focus on three areas: memory consolidation, sleep disorders, and sleep state (mis)perception. Our proposal suggests new directions for sleep and dream science, as well as for the neuroscience of consciousness, and can also inform the diagnosis and treatment of sleep disorders.

The Kantian brain: brain dynamics from a neurophenomenological perspective.

Current research on spontaneous, self-generated brain rhythms and dynamic neural network coordination cast new light on Immanuel Kant's idea of the 'spontaneity' of cognition, that is, the mind's capacity to organize and synthesize sensory stimuli in novel, unprecedented ways. Nevertheless, determining the precise nature of the brain-cognition mapping remains an outstanding challenge. Neurophenomenology, which uses phenomenological information about the variability of subjective experience in order to illuminate the variability of brain dynamics, offers a promising method for addressing this challenge.

Safety of thromboprophylaxis after oncologic head and neck surgery. Study of 1018 patients.

BACKGROUND: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are significantly reduced with appropriate use of thromboprophylaxis and scarcely evaluated in patients undergoing oncologic head and neck surgery (OHNS). METHODS: A retrospective study on 1018 patients who underwent oncologic head and neck surgery. The records of patients with venous thromboembolism (VTE) or postoperative bleeding were reviewed for the cancer grading, management, previous known coagulopathy, anticoagulation, and general demographics. RESULTS: Of a total of 1018 patients undergoing oncologic head and neck surgery, 450 patients had no chemoprophylaxis and 568 received it. The rate of a VTE event in our cohort was 0%. Twelve patients presented with hematoma or bleeding from the surgical site, 11 in the group that received chemoprophylaxis (p = .006). CONCLUSIONS: Our analysis shows no benefit from chemoprophylaxis in oncologic head and neck surgery patients, with no VTE events. Our analysis shows higher rates of morbid side effects from using chemoprophylaxis, and we therefore conclude that chemoprophylaxis should not be routinely used.

Meditation experience predicts introspective accuracy.

The accuracy of subjective reports, especially those involving introspection of one's own internal processes, remains unclear, and research has demonstrated large individual differences in introspective accuracy. It has been hypothesized that introspective accuracy may be heightened in persons who engage in meditation practices, due to the highly introspective nature of such practices. We undertook a preliminary exploration of this hypothesis, examining introspective accuracy in a cross-section of meditation practitioners (1-15,000 hrs experience). Introspective accuracy was assessed by comparing subjective reports of tactile sensitivity for each of 20 body regions during a 'body-scanning' meditation with averaged, objective measures of tactile sensitivity (mean size of body representation area in primary somatosensory cortex; two-point discrimination threshold) as reported in prior research. Expert meditators showed significantly better introspective accuracy than novices; overall meditation experience also significantly predicted individual introspective accuracy. These results suggest that long-term meditators provide more accurate introspective reports than novices.

Affect-biased attention as emotion regulation.

The affective biasing of attention is not typically considered to be a form of emotion regulation. In this article, we argue that 'affect-biased attention' - the predisposition to attend to certain categories of affectively salient stimuli over others - provides an important component of emotion regulation. Affect-biased attention regulates subsequent emotional responses by tuning one's filters for initial attention and subsequent processing. By reviewing parallel research in the fields of emotion regulation and affect-biased attention, as well as clinical and developmental research on individual differences in attentional biases, we provide convergent evidence that habitual affective filtering processes, tuned and re-tuned over development and situation, modulate emotional responses to the world. Moreover, they do so in a manner that is proactive rather than reactive.