Biomarkers represent a critical research area in neurodegeneration disease as they can contribute to studying potential disease-modifying agents, fostering timely therapeutic interventions, and alleviating associated financial costs. Functional connectivity (FC) analysis represents a promising approach to identify early biomarkers in specific diseases. Yet, virtually no study has tested whether potential FC biomarkers prove to be reliable and reproducible across different centers. As such, their implementation remains uncertain due to multiple sources of variability across studies: the numerous international centers capable conducting FC research vary in their scanning equipment and their samples' socio-cultural background, and, more troublingly still, no gold-standard method exists to analyze FC. In this unprecedented study, we aim to address both issues by performing the first multicenter FC research in the behavioral-variant frontotemporal dementia (bvFTD), and by assessing multiple FC approaches to propose a gold-standard method for analysis. We enrolled 52 bvFTD patients and 60 controls from three international clinics (with different fMRI recording parameters), and three additional neurological patient groups. To evaluate FC, we focused on seed analysis, inter-regional connectivity, and several graph-theory approaches. Only graph-theory analysis, based on weighted-matrices, yielded consistent differences between bvFTD and controls across centers. Also, graph metrics robustly discriminated bvFTD from the other neurological conditions. The consistency of our findings across heterogeneous contexts highlights graph-theory as a potential gold-standard approach for brain network analysis in bvFTD. Hum Brain Mapp 38:3804-3822, 2017. © 2017 Wiley Periodicals, Inc.

Background: N,N-dimethyltryptamine is a short-acting psychedelic tryptamine found naturally in many plants and animals. Few studies to date have addressed the neural and psychological effects of N,N-dimethyltryptamine alone, either administered intravenously or inhaled in freebase form, and none have been conducted in natural settings. Aims: Our primary aim was to study the acute effects of inhaled N,N-dimethyltryptamine in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (i.e. “set“ and “setting“), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming N,N-dimethyltryptamine in familiar and comfortable settings. Methods: We combined state-of-the-art wireless electroencephalography with psychometric questionnaires to study the neural and subjective effects of naturalistic N,N-dimethyltryptamine use in 35 healthy and experienced participants. Results: We observed that N,N-dimethyltryptamine significantly decreased the power of alpha (8–12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1–4 Hz) and gamma (30–40 Hz) oscillations. Gamma power increases correlated with subjective reports indicative of some features of mystical-type experiences. N,N-dimethyltryptamine also increased global synchrony and metastability in the gamma band while decreasing those measures in the alpha band. Conclusions: Our results are consistent with previous studies of psychedelic action in the human brain, while at the same time the results suggest potential electroencephalography markers of mystical-type experiences in natural settings, thus highlighting the importance of investigating these compounds in the contexts where they are naturally consumed.

T he insular cortex (InsC) is a main structural-functional hub of the brain.1 It features widespread connections with cortical and subcortical regions, and it is implicated in varied domains, such as body sensation, language, emotion, and social cognition.2 Notably, the InsC abounds in von Economo neurons, which facilitate rapid integration of information. Together with its topological centrality, 1 these features render the InsC as a core region for overall brain dynamics and cognition.InsC damage after stroke or neurodegeneration can considerably impair cognitive function. Stroke can disturb behavioral, emotional, and sensory domains, 3 whereas early neurodegeneration (including the InsC) in behavioral variant frontotemporal dementia (bvFTD) 4 usually leads to social and emotional dysfunction.5 Despite such general differences, little is known about the distinct insular connectivity alterations caused by each of these causes. A direct comparison of InsC connectivity patterns in patients affected by stroke and neurodegeneration 6 may reveal theoretically and clinically relevant differences between each pathophysiological process.In fact, at the molecular level, these conditions differ in timing and physiopathology. Stroke involves tissue loss, neuronal reorganization, and plasticity.7 Instead, neurodegeneration in bvFTD results from protein aggregation, inducing physiopathological events (eg, axonal degeneration, synapse loss, and dendritic retraction) and propagation of misfolded proteins.8 These differences at the molecular level suggest that InsC connectivity may be differentially affected by stroke and bvFTD.Previous studies have reported aberrant long-range connectivity (mostly hypoconnectivity) in both stroke and bvFTD. 4,7 Nevertheless, local connectivity is a key featureBackground and Purpose-Stroke and neurodegeneration cause significant brain damage and cognitive impairment, especially if the insular cortex is compromised. This study explores for the first time whether these 2 causes differentially alter connectivity patterns in the insular cortex. Methods-Resting state-functional magnetic resonance imaging data were collected from patients with insular stroke, patients with behavioral variant frontotemporal dementia, and healthy controls. Data from the 3 groups were assessed through a correlation function analysis. Specifically, we compared decreases in connectivity as a function of voxel Euclidean distance within the insular cortex. Results-Relative to controls, patients with stroke showed faster connectivity decays as a function of distance (hypoconnectivity). In contrast, the behavioral variant frontotemporal dementia group exhibited significant hyperconnectivity between neighboring voxels. Both patient groups evinced global hypoconnectivity. No between-group differences were observed in a volumetrically and functionally comparable region without ischemia or neurodegeneration. Conclusions-Functional insular cortex connectivity is affected differently by cerebral ischemia and neurodegeneration, ...

The use of low sub-perceptual doses of psychedelics (“microdosing”) has gained popularity in recent years. Although anecdotal reports claim multiple benefits associated with this practice, the lack of placebo-controlled studies severely limits our knowledge of microdosing and its effects. Moreover, research conducted in standard laboratory settings could fail to capture the motivation of individuals engaged or planning to engage in microdosing protocols, thus underestimating the likelihood of positive effects on creativity and cognitive function. We recruited 34 individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis), one of the materials most frequently used for this purpose. Following a double-blind placebo-controlled experimental design, we investigated the acute and short-term effects of 0.5 g of dried mushrooms on subjective experience, behavior, creativity (divergent and convergent thinking), perception, cognition, and brain activity. The reported acute effects were significantly more intense for the active dose compared to the placebo, but only for participants who correctly identified their experimental condition. These changes were accompanied by reduced EEG power in the theta band, together with preserved levels of Lempel-Ziv broadband signal complexity. For all other measurements there was no effect of microdosing except for few small changes towards cognitive impairment. According to our findings, low doses of psilocybin mushrooms can result in noticeable subjective effects and altered EEG rhythms, but without evidence to support enhanced well-being, creativity and cognitive function. We conclude that expectation underlies at least some of the anecdotal benefits attributed to microdosing with psilocybin mushrooms.

N,N-Dimethyltryptamine (DMT) is a short acting psychedelic tryptamine found naturally in many plants and animals. When combined with a monoamine oxidase inhibitor, such as in the Amazonian brew known as ayahuasca, DMT becomes orally active and its effects are extended. Few studies to date addressed the neural and psychological effects of DMT alone, either administered intravenously or inhaled in freebase form, and none conducted in natural settings. We combined state-of-the-art wireless electroencephalography (EEG) with psychometric questionnaires to study the acute effects of inhaled DMT in 35 participants in natural settings, focusing on questions tuned to the advantages of conducting field research, including the effects of contextual factors (known as set and setting), the possibility of studying a comparatively large number of subjects, and the relaxed mental state of participants consuming DMT in familiar and comfortable settings. We observed that DMT significantly decreased the power of alpha (8-12 Hz) oscillations throughout all scalp locations, while simultaneously increasing power of delta (1-4 Hz) and gamma (30-40 Hz) oscillations. The pharmacokinetics of inhaled DMT was similar to intravenous administration, but we observed a faster return to baseline for power in the alpha band. Gamma power increases correlated with subjective reports indicative of mystical-type experiences. DMT also increased/decreased global synchrony and metastability in the gamma/alpha band, and resulted in widespread increases in signal complexity measured using the Lempel-Ziv algorithm. These results are consistent with previous studies of psychedelic action in the human brain, while at the same time suggesting potential EEG markers of mystical-type experiences in natural settings. In summary, we conducted one of the first field studies on the neural and psychological effects of a serotonergic psychedelic, yielding new insights and advancing our understanding of the translation between laboratory findings and those obtained in the contexts where these compounds are most frequently consumed.

Dissipative systems evolve in the preferred temporal direction indicated by the thermodynamic arrow of time. The fundamental nature of this temporal asymmetry led us to hypothesize its presence in the neural activity evoked by conscious perception of the physical world, and thus its covariance with the level of conscious awareness. We implemented a data-driven deep learning framework to decode the temporal inversion of electrocorticography signals acquired from non-human primates. Brain activity time series recorded during conscious wakefulness could be distinguished from their inverted counterparts with high accuracy, both using frequency and phase information. However, classification accuracy was reduced for data acquired during deep sleep and under ketamine-induced anesthesia; moreover, the predictions obtained from multiple independent neural networks were less consistent for sleep and anesthesia than for conscious wakefulness. Finally, the analysis of feature importance scores highlighted transitions between slow ($\approx$20 Hz) and fast frequencies (>40 Hz) as the main contributors to the temporal asymmetry observed during conscious wakefulness. Our results show that a preferred temporal direction is manifest in the neural activity evoked by conscious mentation and in the phenomenology of the passage of time, establishing common ground to tackle the relationship between brain and subjective experience.

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In cognitive neurosciences, fundamental principles of mental processes and functional brain organization have been established with highly controlled tasks and testing environments. Recent technical advances allowed the investigation of these functions and their brain mechanisms in naturalistic settings. The diversity in those approaches have been recently (Matusz, P. J., Dikker, S., Huth, A. G., & Perrodin, C. (2019). Are we ready for real‐world neuroscience? Journal of Cognitive Neuroscience, 31(3), 327–338. doi:10.1162/jocn_e_01276) classified via a three‐category cycle, including controlled laboratory, partially naturalistic laboratory, and naturalistic real‐world research. Based on this model, we developed the Multidimensional Assessment of Research in Context (MARC) tool to easily delineate the approach researchers have taken in their study. MARC provides means to describe the degree of ecological validity for each component of a study (e.g., sample, stimuli, measures, etc.), and the study's location on the cycle. The tool comprises seven questions concerning a study's characteristics. It outputs a summary of those and a compass plot, which can be used for presentations, preregistration, grant proposals, and papers. It aims to improve drawing conclusions across studies and raise awareness about the generalizability of research findings.