Psilocybin has shown promise for the treatment of mood disorders, which are often accompanied by cognitive dysfunction including cognitive rigidity. Recent studies have proposed neuropsychoplastogenic effects as mechanisms underlying the enduring therapeutic effects of psilocybin. In an open-label study of 24 patients with major depressive disorder, we tested the enduring effects of psilocybin therapy on cognitive flexibility (perseverative errors on a set-shifting task), neural flexibility (dynamics of functional connectivity or dFC via functional magnetic resonance imaging), and neurometabolite concentrations (via magnetic resonance spectroscopy) in brain regions supporting cognitive flexibility and implicated in acute psilocybin effects (e.g., the anterior cingulate cortex, or ACC). Psilocybin therapy increased cognitive flexibility for at least 4 weeks post-treatment, though these improvements were not correlated with the previously reported antidepressant effects. One week after psilocybin therapy, glutamate and N-acetylaspartate concentrations were decreased in the ACC, and dFC was increased between the ACC and the posterior cingulate cortex (PCC). Surprisingly, greater increases in dFC between the ACC and PCC were associated with less improvement in cognitive flexibility after psilocybin therapy. Connectome-based predictive modeling demonstrated that baseline dFC emanating from the ACC predicted improvements in cognitive flexibility. In these models, greater baseline dFC was associated with better baseline cognitive flexibility but less improvement in cognitive flexibility. These findings suggest a nuanced relationship between cognitive and neural flexibility. Whereas some enduring increases in neural dynamics may allow for shifting out of a maladaptively rigid state, larger persisting increases in neural dynamics may be of less benefit to psilocybin therapy.

The MEGA‐PRESS‐IVS method has been developed, which combines MEGA (a frequency‐selective editing technique) editing with the point‐resolved spectroscopy sequence (PRESS) and inner volume saturation (IVS) localization, reducing the deleterious effects of spatial variation in coupling evolution. The IVS method has been previously described for improved efficiency of lactate detection. The current study demonstrates that the combination of MEGA‐PRESS with IVS results in increased sensitivity for edited single‐voxel measurements of glutamate and γ‐aminobutyric acid (GABA). A four‐compartment model of coupling evolution is investigated through simple product operators and full spin‐system simulations and the predicted pattern of signal evolution is demonstrated through MEGA‐PRESS‐MRSI. MEGA‐PRESS‐IVS is then compared to MEGA‐PRESS in a phantom and an average signal increase of 24% is demonstrated in five healthy volunteers. Magn Reson Med, 2007.

A method is described that allows the in vivo differentiation of N‐acetyl aspartate (NAA) from N‐acetyl aspartyl glutamate (NAAG) by in vivo MR spectroscopy (MRS) at 3 Tesla (3T). The method, which is based on MEGA‐point‐resolved spectroscopy (PRESS) editing, selectively targets the aspartyl spin system of one species while deliberately removing the other species from the spectrum. This allows quantitative measurements of NAA and NAAG without the need for fitting of unresolved peaks. White matter concentrations of NAA (6.7 ± 0.3 mM) and NAAG (2.2 ± 0.3 mM) were measured in 10 healthy volunteers to demonstrate the method. Magn Reson Med 57:977–982, 2007.

Purpose: To evaluate the reproducibility of spectroscopic measurements from the anterior cingulate (AC) and the dorsolateral prefrontal cortex (DLPFC) regions at 7T using a 32‐channel head coil.Materials and Methods: Spectra were acquired in four healthy subjects each scanned twice using a stimulated echo acquisition mode (STEAM) sequence, and a MEGA‐PRESS‐IVS sequence for gamma‐aminobutyric acid (GABA) editing. STEAM spectra were quantified using LCModel, whereas MEGA‐PRESS‐IVS data were analyzed using peak integrals determined using in‐house software. Mean coefficient of variation (CV) and mean absolute difference between visits were calculated.Results: For the AC STEAM dataset, the mean CV between visits was 6.2% for prominent metabolites such as N‐acetylaspartate (NAA), total creatine (tCr), and total choline (tCho) and 6.3% for low signal‐to‐noise ratio (SNR) metabolites such as glutamate (Glu), glutamine (Gln), and GABA. The mean CV between visits for the DLPFC STEAM dataset was 8.5% for prominent metabolites and 21% for lower SNR metabolites. In the AC, the reproducibility measures for GABA were superior for STEAM compared to MEGA‐PRESS‐IVS (mean CV of 3.5% vs. 13.6%), but the opposite pattern was observed in the DLPFC region (mean CV of 16.2% vs. 13.4%).Conclusion: 7T MR spectroscopy of the AC and DLPFC using both short TE STEAM and MEGA‐PRESS‐IVS sequences provide excellent reproducibility of 12 metabolites, including GABA. J. Magn. Reson. Imaging 2013;38:460–467.