There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one’s self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.

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Creativity is an essential cognitive ability linked to all areas of our everyday functioning. Thus, finding a way to enhance it is of broad interest. A large number of anecdotal reports suggest that the consumption of psychedelic drugs can enhance creative thinking; however, scientific evidence is lacking. Following a double-blind, placebo-controlled, parallel-group design, we demonstrated that psilocybin (0.17 mg/kg) induced a time- and construct-related differentiation of effects on creative thinking. Acutely, psilocybin increased ratings of (spontaneous) creative insights, while decreasing (deliberate) task-based creativity. Seven days after psilocybin, number of novel ideas increased. Furthermore, we utilized an ultrahigh field multimodal brain imaging approach, and found that acute and persisting effects were predicted by within- and between-network connectivity of the default mode network. Findings add some support to historical claims that psychedelics can influence aspects of the creative process, potentially indicating them as a tool to investigate creativity and subsequent underlying neural mechanisms. Trial NL6007; psilocybin as a tool for enhanced cognitive flexibility; https://www.trialregister.nl/trial/6007.

PurposeIn order to fully benefit from the improved signal‐to‐noise and contrast‐to‐noise ratios at 9.4T, the challenges of normalB1+ inhomogeneity and the long acquisition time of high‐resolution 2D gradient‐recalled echo (GRE) imaging were addressed.Theory and MethodsFlip angle homogenized excitations were achieved by parallel transmission (pTx) of 3‐spoke pulses, designed by magnitude least‐squares optimization in a slice‐by‐slice fashion; the acquisition time reduction was achieved by simultaneous multislice (SMS) pulses. The slice‐specific spokes complex radiofrequency scaling factors were applied to sinc waveforms on a per‐channel basis and combined with the other pulses in an SMS slice group to form the final SMS‐pTX pulse. Optimal spokes locations were derived from simulations.ResultsFlip angle maps from presaturation TurboFLASH showed improvement of flip angle homogenization with 3‐spoke pulses over CP‐mode excitation (normalized root‐mean‐square error [NRMSE] 0.357) as well as comparable excitation homogeneity across the single‐band (NRMSE 0.119), SMS‐2 (NRMSE 0.137), and SMS‐3 (NRMSE 0.132) 3‐spoke pulses. The application of the 3‐spoke SMS‐3 pulses in a 48‐slice GRE protocol, which has an in‐plane resolution of 0.28 × 0.28 mm, resulted in a 50% reduction of scan duration (total acquisition time 6:52 min including reference scans).ConclusionTime‐efficient flip angle homogenized high‐resolution GRE imaging at 9.4T was accomplished by using slice‐specific SMS‐pTx spokes excitations. Magn Reson Med 78:1050–1058, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.