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The article of record as published may be found at https://doi.org/10.1016/j.mehy.2019.109523 Conscious Action Theory extends quantum theory to macroscopic phenomena and suggests physical correlates of consciousness occur at the intersection of external measurement signals and internally generated signals from memories that model the outside world. This physical theory predicts conscious phenomena happen at all scales and differ only by the size and complexity of material organizations involved. At the scale of the human "Brain" consciousness is predicted to happen where the processing loop of activity in the Glial network interfaces with the real world input-output processing loop of the Nuronal network. This happens at the Tripartite synapses creating an intersection plenum in biological systems that produces the experience of empty space and the objects it contains. Analysis of the transmitter-receptor strengths implementing the control and feedback be- tween the Glial and Neuronal networks indicate imbalances can be directly related to schizophrenia, mania, epilepsy, and depression. This paper addresses three topics supporting the above mechanisms for normal consciousness functioning and its medical deviations. First we preset the architecture of a pan-psychic physical theory, which supports the hypothesis that tri-partite synapses are the location of human conscious experience. Second we discuss the inner workings of the Glial network to support long term memory and control functions corresponding to the inner feeling of the "I" self. Third, we consider the relation between psychiatric conditions and the balance states between the number of neuronal transmitters and astrocytic receptors.

Recent brain imaging studies suggest that semantic processing of words and images may share a common neural network, although modality-specific activation can also be observed. Other studies using event-related potentials (ERPs) report that brain responses to words and images may already differ at ~150 ms following stimulus presentation. The question thus remains, which differences are due to perceptual categorization processes and which differences are due to the semantic ones? Using ERP recordings and spatio-temporal source localization analysis, we investigated the dynamics of brain activation during a recognition task. The stimuli consisted of a randomized set of verbal (words vs. non-words) and pictorial items (line drawings of objects vs. scrambled drawings). After each stimulus, subjects had to decide whether it corresponds to a recognizable word or objects. ERP map series were first analyzed in terms of segments of quasi-stable map topography using a cluster analysis. This showed that verbal and pictorial stimuli elicited different field patterns in two time segments between ~190-400 ms. Before and after this period, map patterns were similar between verbal and pictorial conditions indicating that the same brain structures were engaged during the early and late steps of processing. Source localization analysis of map segments corresponding to the P100 and the N150 components first showed activation of posterior bilateral regions and then of left temporo-posterior areas. During the period differentiating conditions, other patterns of activation, involving mainly left anterior and posterior regions for words and bilateral posterior regions for images, were observed. These findings suggest that, while sharing an initial common network, recognition of verbal and pictorial stimuli subsequently engage different brain regions during time periods generally allocated to the semantic processing of stimuli.

Abstract During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

Objective: To assess the time course of recovery of severely abnormal initial amplitude integrated electroencephalographic (aEEG) patterns (flat trace (FT), continuous low voltage (CLV), or burst suppression (BS)) in full term asphyxiated neonates, in relation to other neurophysiological and neuroimaging findings and neurodevelopmental outcome. Methods: A total of 190 aEEGs of full term infants were reviewed. The neonates were admitted within 6 hours of birth to the neonatal intensive care unit because of perinatal asphyxia, and aEEG recording was started immediately. In all, 160 infants were included; 65 of these had an initial FT or CLV pattern and 25 an initial BS pattern. Neurodevelopmental outcome was assessed using a full neurological examination and the Griffiths’ mental developmental scale. Results: In the FT/CLV group, the background pattern recovered to continuous normal voltage within 24 hours in six of the 65 infants (9%). All six infants survived the neonatal period; one had a severe disability, and five were normal at follow up. In the BS group, the background pattern improved to normal voltage in 12 of the 25 infants (48%) within 24 hours. Of these infants, one died, five survived with moderate to severe disability, two with mild disability, and four were normal. The patients who did not recover within 24 hours either died in the neonatal period or survived with a severe disability. Conclusion: In this study there was a small group of infants who presented with a severely abnormal aEEG background pattern within six hours of birth, but who achieved recovery to a continuous normal background pattern within the first 24 hours. Sixty one percent of these infants survived without, or with a mild, disability.

Aerobic exercise has been shown to impact brain structure and cognition in children and adults. Exercise-induced activation of a growth protein known as brain derived neurotrophic factor (BDNF) is thought to contribute to such relationships. To date, however, no study has examined how aerobic fitness relates to cortical brain structure during development and if BDNF genotype moderates these relationships. Using structural magnetic resonance imaging (MRI) and FreeSurfer, the current study examined how aerobic fitness relates to volume, thickness, and surface area in 34 male adolescents, 15 to 18 years old. Moreover, we examined if the val66met BDNF genotype moderated these relationships. We hypothesized that aerobic fitness would relate to greater thickness and volumes in frontal, parietal, and motor regions, and that these relationships would be less robust in individuals carrying a Met allele, since this genotype leads to lower BDNF expression. We found that aerobic fitness positively related to right rostral middle frontal cortical volume in all adolescents. However, results also showed BDNF genotype moderated the relationship between aerobic fitness and bilateral medial precuneus surface area, with a positive relationship seen in individuals with the Val/Val allele, but no relationship detected in those adolescents carrying a Met allele. Lastly, using self-reported levels of aerobic activity, we found that higher-fit adolescents showed larger right medial pericalcarine, right cuneus and left precuneus surface areas as compared to their low-fit peers. Our findings suggest that aerobic fitness is linked to cortical brain development in male adolescents, and that more research is warranted to determine how an individual’s genes may influence these relationships.

AbstractFocused ultrasound and microbubble (FUS + MB)-mediated blood–brain barrier (BBB) permeability enhancement can facilitate targeted brain-drug delivery. While controlling the magnitude of BBB permeability enhancement is necessary to limit tissue damage, little work has attempted to decouple these concepts. This work investigated the relationship between BBB permeability enhancement and the relative transcription of inflammatory mediators 4 h following sonication. Three microbubble formulations, Definity, BG8774, and MSB4, were compared, with the dose of each formulation normalized to gas volume. While changes in the transcription of key proinflammatory mediators, such as Il1b, Ccl2, and Tnf, were correlated to the magnitude of BBB permeability enhancement, these correlations were not independent of microbubble formulation; microbubble size distribution may play an important role, as linear regression analyses of BBB permeability magnitude versus differential gene expression for these proinflammatory mediators revealed significantly greater slopes for MSB4, a monodisperse microbubble with mean diameter of 4 μm, compared to Definity or BG8774, both polydisperse microbubbles with mean diameters below 2 μm. Additionally, the function of an acoustic feedback control algorithm, based on the detection threshold of ultraharmonic emissions, was assessed. While this control strategy was effective in limiting both wideband emissions and red blood cell extravasation, microbubble formulation was found to influence the magnitude of BBB leakage and correlations to acoustic emissions. This work demonstrates that while the initial magnitude of FUS + MB-mediated BBB permeability enhancement has a clear influence on the subsequent inflammatory responses, microbubble characteristics influence these relationships and must also be considered.

Intracranial infection of Theiler’s murine encephalomyelitis virus (TMEV) induces demyelination and a neurological disease in susceptible SJL/J (SJL) mice that resembles multiple sclerosis. While the virus is cleared from the central nervous system (CNS) of resistant C57BL/6 (B6) mice, it persists in SJL mice. To investigate the role of viral persistence and its accompanying immune responses in the development of demyelinating disease, transgenic mice expressing the P1 region of the TMEV genome (P1-Tg) were employed. Interestingly, P1-Tg mice with the B6 background showed severe reductions in both CD4 and CD8 T-cell responses to capsid epitopes, while P1-Tg mice with the SJL background displayed transient reductions following viral infection. Reduced antiviral immune responses in P1-Tg mice led to >100- to 1,000-fold increases in viral persistence at 120 days postinfection in the CNS of mice with both backgrounds. Despite the increased CNS TMEV levels in these P1-Tg mice, B6 P1-Tg mice developed neither neuropathological symptoms nor demyelinating lesions, and SJL P1-Tg mice developed significantly less severe TMEV-induced demyelinating disease. These results strongly suggest that viral persistence alone is not sufficient to induce disease and that the level of T-cell immunity to viral capsid epitopes is critical for the development of demyelinating disease in SJL mice. Theiler’s murine encephalomyelitis virus (TMEV) is a member of the Cardiovirus genus within the Picornaviridae family. TMEV is a common enteric pathogen among wild mice and rarely causes a neurological disease. However, intracerebral (i.c.) infection in susceptible mice, e.g., SJL/J (SJL) mice, reproducibly induces a chronic immune-mediated demyelinating disease, providing an excellent infectious model for multiple sclerosis (10, 25). The precise mechanism of TMEV-induced demyelinating disease (TMEV-IDD) is unknown. However, virus-specific T cells, various proinflammatory chemokines (e.g., monocyte chemoattractant protein 1 and interferon-inducible protein 10), and cytokines (e.g., gamma interferon [IFN-] and tumor necrosis factor alpha) in the central nervous system (CNS) are believed to play a critical role (reviewed in references 26 and 44) in this disease process. In addition, the presence of persistent viral infection may lead to demyelinating disease by directly causing host cell lysis (51), which releases sequestrated CNS autoantigens, resulting in the activation of autoreactive T cells (39). The persistence of viral antigens also is believed to perpetuate a massive inflammatory milieu in the CNS by continuously activating virus-specific T cells (25, 33). Thus, it is conceivable that viral persistence is essential for the development of TMEV-IDD. This possibility is consistent with the observation that spontaneously occurring variant viruses with relatively low pathogenicity display reduced levels of viral persistence in the CNS (27), implying that viral persistence is a critical susceptibility factor. Furthermore, genetic studies show that viral persistence levels in the CNS correlate with demyelinating disease levels (7, 34).

Abstract As potential new ligands targeting the binding site of γ-aminobutyric acid (GABA) receptor ionophore, trans -5- tert -butyl-2-(4′-fluoropropynylphenyl)-2-methyl-1,1-dioxo-1,3-dithiane (1) and cis / trans -5- tert -butyl-2-(4′-fluoropropynylphenyl)-2-methyl-1,1,3,3-tetroxo-1,3-dithiane (2) were selected for radiolabeling and initial evaluation as in vivo imaging agents for positron emission tomography (PET). Both compounds exhibited identical high in vitro binding affinities ( K i =6.5 nM). Appropriate tosylate-substituted ethynyl precursors were prepared by multistep syntheses involving stepwise sulfur oxidation and chromatographic isolation of desired trans isomers. Radiolabeling was accomplished in one step using nucleophilic [ 18 F]fluorination. In vivo biodistribution studies with trans -[ 18 F] 1 and trans -[ 18 F]2 showed significant initial uptake into mouse brain and gradual washout, with heterogeneous regional brain distributions and higher retention in the cerebral cortex and cerebellum and lower retention in the striatum and pons–medulla. These regional distributions of the new radioligands correlated with in vitro and ex vivo measures of standard radioligands binding to the ionophore- and benzodiazepine-binding sites of GABA A receptor in rodent brain. A comparison of these results with previously prepared radiotracers for other neurochemical targets, including successes and failures as in vivo radioligands, suggests that higher-affinity compounds with increased retention in target brain tissues will likely be needed before a successful radiopharmaceutical for human PET imaging can be identified.