Decoupling of cortical activity from behavioral state following administration of the classic psychedelic DOI.

Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit basis for the alterations in experience caused by CPs requires further study. The medial prefrontal cortex (mPFC), where CPs have been shown to induce rapid, 5-HT2A receptor-dependent structural and neurophysiological changes, is believed to be a key site of action. To investigate the acute neural circuit changes induced by CPs, we recorded single neurons and local field potentials in the mPFC of freely behaving male mice after administration of the 5-HT2A/2C receptor-selective CP, 2,5-Dimethoxy-4-iodoamphetamine (DOI). We segregated recordings into active and rest periods in order to examine cortical activity during desynchronized (active) and synchronized (rest) states. We found that DOI induced a robust decrease in low frequency power when animals were at rest, attenuating the usual synchronization that occurs during less active behavioral states. DOI also increased broadband gamma power and suppressed activity in fast-spiking neurons in both active and rest periods. Together, these results suggest that the CP DOI induces persistent desynchronization in mPFC, including during rest when mPFC typically exhibits more synchronized activity. This shift in cortical dynamics may in part underlie the longer-lasting effects of CPs on plasticity, and may be critical to their therapeutic properties.

Estimating Intrinsic Manifold Dimensionality to Classify Task-Related Information in Human and Non-Human Primate Data.

Feature selection, or dimensionality reduction, has become a standard step in reducing large-scale neural datasets into usable signals for brain-machine interface and neurofeedback decoders. Current techniques in fMRI data reduce the number of voxels (features) by performing statistics on individual voxels or using traditional techniques that utilize linear combinations of features (e.g., principal component analysis (PCA)). However, these methods often do not account for the cross-correlations found across voxels and do not sufficiently reduce the feature space to support efficient real-time feedback. To overcome these limitations, we propose using factor analysis on fMRI data. This technique has become increasingly popular for extracting a minimal number of latent features to explain high-dimensional data in non-human primates (NHPs). Here, we demonstrate these methods in both NHP and human data. In NHP subjects (n=2), we reduced the number of features to an average of 26.86% and 14.86% of the total feature space to build our multinomial classifier. In one NHP subject, the average accuracy of classifying eight target locations over 64 sessions was 62.43% (+/-6.19%) compared to a PCA-based classifier with 60.26% (+/-6.02%). In healthy fMRI subjects, we reduced the feature space to an average of 0.33% of the initial space. Group average (n=5) accuracy of FA-based category classification was 74.33% (+/- 4.91%) compared to a PCA-based classifier with 68.42% (+/-4.79%). FA-based classifiers can maintain the performance fidelity observed with PCA-based decoders. Importantly, FA-based methods allow researchers to address specific hypotheses about how underlying neural activity relates to behavior.