Diffusion functional MRI reveals global brain network functional abnormalities driven by targeted local activity in a neuropsychiatric disease mouse model.

Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as an alternative functional imaging method to detect brain activity without confounding hemodynamic effects. Here, taking advantage of this DfMRI feature, we investigated abnormalities of dynamic brain function in a neuropsychiatric disease mouse model (glial glutamate transporter-knockdown mice with obsessive-compulsive disorder [OCD]-related behavior). Our DfMRI approaches consisted of three analyses: resting state brain activity, functional connectivity, and propagation of neural information. We detected hyperactivation and biased connectivity across the cortico-striatal-thalamic circuitry, which is consistent with known blood oxygen-level dependent (BOLD)-fMRI patterns in OCD patients. In addition, we performed ignition-driven mean integration (IDMI) analysis, which combined activity and connectivity analyses, to evaluate neural propagation initiated from brain activation. This analysis revealed an unbalanced distribution of neural propagation initiated from intrinsic local activation to the global network, while these were not detected by the conventional method with BOLD-fMRI. This abnormal function detected by DfMRI was associated with OCD-related behavior. Together, our comprehensive DfMRI approaches can successfully provide information on dynamic brain function in normal and diseased brains.

Optogenetic activation of dorsal raphe serotonin neurons induces brain-wide activation.

Serotonin is a neuromodulator that affects multiple behavioral and cognitive functions. Nonetheless, how serotonin causes such a variety of effects via brain-wide projections and various receptors remains unclear. Here we measured brain-wide responses to optogenetic stimulation of serotonin neurons in the dorsal raphe nucleus (DRN) of the male mouse brain using functional MRI with an 11.7 T scanner and a cryoprobe. Transient activation of DRN serotonin neurons caused brain-wide activation, including the medial prefrontal cortex, the striatum, and the ventral tegmental area. The same stimulation under anesthesia with isoflurane decreased brain-wide activation, including the hippocampal complex. These brain-wide response patterns can be explained by DRN serotonergic projection topography and serotonin receptor expression profiles, with enhanced weights on 5-HT1 receptors. Together, these results provide insight into the DR serotonergic system, which is consistent with recent discoveries of its functions in adaptive behaviors.

Autonomous, bidding, credible, decentralized, ethical, and funded (ABCDEF) publishing.

Scientists write research articles, process ethics reviews, evaluate proposals and research, and seek funding. Several strategies have been proposed to optimize these operations and to decentralize access to research resources and opportunities. For instance, we previously proposed the trinity review method, combining registered reports with financing and research ethics assessments. However, previously proposed systems have a number of shortcomings, including how to implement them, e.g., who manages them, how incentives for reviewers are paid, etc. Various solutions have been proposed to address these issues, employing methods based on blockchain technologies, called "decentralized science (DeSci)". Decentralized approaches that exploit these developments offer potentially profound improvements to the troubled scientific ecosystem. Here, we propose a system that integrates ethics reviews, peer reviews, and funding in a decentralized manner, based on Web3 technology. This new method, named ABCDEF publishing, would enhance the speed, fairness, and transparency of scientific research and publishing.

Functions of consciousness: conceptual clarification.

There are many theories of the functions of consciousness. How these theories relate to each other, how we should assess them, and whether any integration of them is possible are all issues that remain unclear. To contribute to a solution, this paper offers a conceptual framework to clarify the theories of the functions of consciousness. This framework consists of three dimensions: (i) target, (ii) explanatory order, and (iii) necessity/sufficiency. The first dimension, target, clarifies each theory in terms of the kind of consciousness it targets. The second dimension, explanatory order, clarifies each theory in terms of how it conceives of the explanatory relation between consciousness and function. The third dimension, necessity/sufficiency, clarifies each theory in terms of the necessity/sufficiency relation posited between consciousness and function. We demonstrate the usefulness of this framework by applying it to some existing scientific and philosophical theories of the functions of consciousness.

TOB is an effector of the hippocampus-mediated acute stress response.

Stress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood. Transducer of ErbB2.1, known as TOB, is involved in different physiological functions, including cellular stress and immediate response to stimulation. In this study, we investigated the role of TOB in psychological stress machinery at molecular, neural circuit, and behavioral levels. Interestingly, TOB protein levels increased after mice were exposed to acute stress. At the neural circuit level, functional magnetic resonance imaging (fMRI) suggested that intra-hippocampal and hippocampal-prefrontal connectivity were dysregulated in Tob knockout (Tob-KO) mice. Electrophysiological recordings in hippocampal slices showed increased postsynaptic AMPAR-mediated neurotransmission, accompanied by decreased GABA neurotransmission and subsequently altered Excitatory/Inhibitory balance after Tob deletion. At the behavioral level, Tob-KO mice show abnormal, hippocampus-dependent, contextual fear conditioning and extinction, and depression-like behaviors. On the other hand, increased anxiety observed in Tob-KO mice is hippocampus-independent. At the molecular level, we observed changes in factors involved in stress response like decreased stress-induced LCN2 expression and ERK phosphorylation, as well as increased MKP-1 expression. This study introduces TOB as an important modulator in the hippocampal stress signaling machinery. In summary, we reveal a molecular pathway and neural circuit mechanism by which Tob deletion contributes to expression of pathological stress-related behavior.

A new experimental phenomenological method to explore the subjective features of psychological phenomena: its application to binocular rivalry.

The subjective features of psychological phenomena have been studied intensively in experimental science in recent years. Although various methods have been proposed to identify subjective features of psychological phenomena, there are elusive subjective features such as the spatiotemporal structure of experience, which are difficult to capture without some additional methodological tools. We propose a new experimental method to address this challenge, which we call the contrast-based experimental phenomenological method (CEP). CEP proceeds in four steps: (i) front-loading phenomenology, (ii) online second-personal interview, (iii) questionnaire survey, and (iv) hypotheses testing. It differs from other experimental phenomenological methods in that it takes advantage of phenomenal contrasts in collecting phenomenological data. In this paper, we verify the validity and productivity of this method by applying it to binocular rivalry (BR). The study contributes to empirical research on BR in three respects. First, it provides additional evidence for existing propositions about the subjective features of BR: e.g. the proposition that the temporal dynamics of the experience depend upon subject-dependent parameters such as attentional change. Second, it deepens our understanding of the spatiotemporal structures of the transition phase of BR. Third, it elicits new research questions about depth experience and individual differences in BR. The presence of such contributions demonstrates the validity and productivity of CEP.