Functional connectivity analysis, using independent component analysis, of the data from a 2012 study (Carhart-Harris et al., 2012), revealed increased DMN and task positive network (TPN) functional connectivity, therefore showing a decrease in DMN-TPN orthogonality after psilocybin (Carhart-Harris et al., 2013). Carhart-Harris et al. propose that increased DMN-TPN coupling in the presence of preserved thalamocortical connectivity is related to a state in which arousal is preserved but the distinction between inner thought and external focus becomes blurred.
Tagliazucchi et al. (2014) carried out a reanalysis of the previously published data from Carhart-Harris et al. (2012). Their new analyses were prompted by a view that more sensitive and specific indices might help to develop a better understanding of the neurobiology of conscious states, and specifically that measures that include variance over time might be especially informative. They note that the brain has been described as a system resting in (or near) a critical point or transition zone between states of order and disorder (see references in Tagliazucchi et al., 2014). They therefore tested the hypothesis that the brain can explore a maximal repertoire of its possible dynamic states in this critical zone, asking the question as to whether changes in spontaneous brain activity produced by psilocybin were consistent with displacement from this critical point, possibly moving toward a more entropic or supercritical state (Carhart-Harris et al., 2014). To test this hypothesis, the authors focused on variability in activity and functional connectivity parameters over time and presented empirical data that tested the hypothesis that brain activity becomes less ordered in the psychedelic state, with enhancement of the repertoire of possible states. The power spectrum density of the spectral content of spontaneous BOLD fluctuations can be characterized by a single parameter α, which condenses the scaling behavior and is demonstrative of the long-range temporal correlations of any given signal. Both BOLD signal variance and total spectral power measures showed increased variability after psilocybin, both in the temporal and spectral domain, with peaks in the ACC and bilateral hippocampus.
One of the strategies that has been used for adoptive immunotherapy of cancer identifies, isolates, and expands in vitro CD8+ T-cells responsive to human tumours antigens. However, few immunotherapeutic approaches that target the recruitment of tumor reactive CD8+ T cells have been effective against solid tumors. Surely, tumors of the CNS provide a unique challenge to immunotherapy due to more stringent regulation of lymphocyte circulation and the potential for the negative side effects induced by T-cell effector functions. In 2008, a mouse model of autochthonous brain cancer to assess adoptive immunotherapeutic approaches of polyomavirus-induced disease was examined. This model consisted of SV40 LTAg transgenic mice SV11 which develop spontaneous choroid plexus tumors due to expression of full-length LTAg and lack the endogenous CD8+ T cells that in nontransgenic mice respond to the three different LTAg epitopes, I, II/III, and IV. In the model, donor T cells against the immunodominant epitope IV are subject to the potential effects of peripheral tolerance and the immunosuppressive tumor environment following adoptive transfer into SV11 mice with both minimal disease and advanced stage tumors. The performed experiments demonstrated that LTAg-specific CD8+ T cells from immune donors accumulated at the tumor site and are associated with reduced tumor burden and extension of the lifespan. In addition, it has been shown that IFN-gamma component donor cells play a major role in the immune-mediated control of established autochthonous tumors in CNS [87, 88].
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