Business Improvement Districts in the UK: Territorialising a ‘global’ model?

Noninvasive transcranial brain stimulation (NTBS) is widely used to elucidate the contribution of different brain regions to various cognitive functions. Here we present three modeling approaches that are informed by functional or structural brain mapping or behavior profiling and discuss how these approaches advance the scientific potential of NTBS as an interventional tool in cognitive neuroscience. (i) Leveraging the anatomical information provided by structural imaging, the electric field distribution in the brain can be modeled and simulated. Biophysical modeling approaches generate testable predictions regarding the impact of interindividual variations in cortical anatomy on the injected electric fields or the influence of the orientation of current flow on the physiological stimulation effects. (ii) Functional brain mapping of the spatiotemporal neural dynamics during cognitive tasks can be used to construct causal network models. These models can identify spatiotemporal changes in effective connectivity during distinct cognitive states and allow for examining how effective connectivity is shaped by NTBS. (iii) Modeling the NTBS effects based on neuroimaging can be complemented by behavior-based cognitive models that exploit variations in task performance. For instance, NTBS-induced changes in response speed and accuracy can be explicitly modeled in a cognitive framework accounting for the speed–accuracy trade-off. This enables to dissociate between behavioral NTBS effects that emerge in the context of rapid automatic responses or in the context of slow deliberate responses. We argue that these complementary modeling approaches facilitate the use of NTBS as a means of dissecting the causal architecture of cognitive systems of the human brain

Comparative Review of Microglia and Monocytes in CNS Phagocytosis

Macrophages maintain tissue homeostasis by phagocytosing and removing unwanted materials such as dead cells and cell debris. Microglia, the resident macrophages of the central nervous system (CNS), are no exception. In addition, a series of recent studies have shown that microglia phagocytose the neuronal synapses that form the basis of neural circuit function. This discovery has spurred many neuroscientists to study microglia. Importantly, in the CNS parenchyma, not only microglia but also blood-derived monocytes, which essentially differentiate into macrophages after infiltration, exert phagocytic ability, making the study of phagocytosis in the CNS even more interesting and complex. In particular, in the diseased brain, the phagocytosis of tissue-damaging substances, such as myelin debris in multiple sclerosis (MS), has been shown to be carried out by both microglia and blood-derived monocytes. However, it remains largely unclear why blood-derived monocytes need to invade the parenchyma, where microglia are already abundant, to assist in phagocytosis. We will also discuss whether this phagocytosis can affect the fate of the phagocytosing cell itself as well as the substance being phagocytosed and the surrounding environment in addition to future research directions. In this review, we will introduce recent studies to answer a question that often arises when studying microglial phagocytosis: under what circumstances and to what extent blood-derived monocytes infiltrate the CNS and contribute to phagocytosis. In addition, the readers will learn how recent studies have experimentally distinguished between microglia and infiltrating monocytes. Finally, we aim to contribute to the progress of phagocytosis research by discussing the effects of phagocytosis on phagocytic cells

Synaptic Pruning by Microglia in Epilepsy

Structural and functional collapse of the balance between excitatory (E) and inhibitory (I) synapses, i.e., synaptic E/I balance, underlies the pathogeneses of various central nervous system (CNS) disorders. In epilepsy, the synaptic E/I balance tips toward excitation; thus, most of the existing epileptic remedies have focused on how to directly suppress the activity of neurons. However, because as many as 30% of patients with epilepsy are drug resistant, the discovery of new therapeutic targets is strongly desired. Recently, the roles of glial cells in epilepsy have gained attention because glial cells manipulate synaptic structures and functions in addition to supporting neuronal survival and growth. Among glial cells, microglia, which are brain-resident immune cells, have been shown to mediate inflammation, neuronal death and aberrant neurogenesis after epileptic seizures. However, few studies have investigated the involvement of synaptic pruning—one of the most important roles of microglia—in the epileptic brain. In this review, we propose and discuss the hypothesis that synaptic pruning by microglia is enhanced in the epileptic brain, drawing upon the findings of previous studies. We further discuss the possibility that aberrant synaptic pruning by microglia induces synaptic E/I imbalance, promoting the development and aggravation of epilepsy

Differentiation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neurons in Mouse Hippocampal Slice Cultures

Potential clinical applications of neurons derived from human induced pluripotent stem cells (hiPSC-neurons) for drug screening and transplantation therapies have received considerable attention. However, it remains unclear whether and how transplanted hiPSC-neurons are incorporated into pre-existing neural circuits. Here we developed a co-culture system of hiPSC-neurons and mouse hippocampal slices to examine the differentiation of hiPSC-neurons in pre-existing neural circuits. hiPSC-neurons transplanted in mouse hippocampal slices expressed the hippocampal neuron-specific markers HuB and Prox1 after 7 days of culture, while those markers were scarcely expressed in hiPSC-neurons cultured on glass dishes. Furthermore, hiPSC-neurons transplanted in the dentate gyrus (DG) of slice cultures grew to exhibit dentate granule cell-like morphologies, including besom-shaped dendrites. Similarly, hiPSC-neurons transplanted in the CA1 region of slice cultures grew to exhibit CA1 pyramidal cell-like morphologies, including primary apical and multiple basal dendrites with synaptic spines. Additionally, these cells projected axons toward the entorhinal cortex (EC) as observed in vivo. These data suggest that hiPSC-neurons were anatomically integrated into pre-existing neural circuits in a region-specific manner. Thus, the co-culture system will be useful for the study of efficient strategies to differentiate transplanted hiPSC-neurons

Supplementary_file_AJHPM-2017-12-241_(Kanno_Y)_(1) - Validity and Reliability of the Dying Care Process and Outcome Scales Before and After Death From the Bereaved Family Members’ Perspective

<p>Supplementary_file_AJHPM-2017-12-241_(Kanno_Y)_(1) for Validity and Reliability of the Dying Care Process and Outcome Scales Before and After Death From the Bereaved Family Members’ Perspective by Yusuke Kanno, Kazuki Sato, Megumi Shimizu, Yuko Funamizu, Hideaki Andoh, Megumi Kishino, Tomomi Senaga, Tetsu Takahashi, and Mitsunori Miyashita in American Journal of Hospice and Palliative Medicine®</p