Biology subjects

Coleman, C. R.

Publications and source records attributed to Coleman, C. R..

4 recordsLinked to original sources

bioRxiv2025

LSD reconfigures the frequency-specific network landscape of the human brain

Lysergic acid diethylamide (LSD) and other psychedelic substances profoundly alter human consciousness. While several studies have demonstrated changes in brain function and connectivity associated with psychedelics, we still have a limited understanding of how LSD reshapes brain networks operating across different frequency bands. In this study, we applied the recently developed FREQ-NESS method to MEG data from 14 healthy participants who received LSD under four conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. LSD significantly restructures canonical networks in the alpha and beta bands. Relative to broadband brain activity, it enhances the prominence of high alpha (12.1, 13.3 Hz) across all experimental conditions and high beta (25.3 Hz) in three conditions. Conversely, LSD decreases the prominence of low beta (18.1, 19.3 Hz) in both Open and Closed conditions and low alpha (8.5 Hz) in the latter. In addition, LSD substantially alters the spatial distributions or topographies of the networks. Under LSD, the low alpha (8.5 Hz) network shifts anteriorly toward the motor cortex, while high alpha (12.1, 13.3 Hz) becomes more localized to the visual cortex. Low beta (18.1, 19.3 Hz) expands over the temporal and occipital cortices, whereas high beta (25.3, 26.5 Hz) topographies remain unchanged. Our findings provide critical insights into the specific frequencies and spatial networks in which LSD modulates brain connectivity, adding nuance to prevailing theories about network disintegration under psychedelics. Significance statementPsychedelic substances such as lysergic acid diethylamide (LSD) profoundly alter perception and cognition, yet their effect on brain activity across different frequency bands remains unclear. Using FREQ-NESS applied to MEG data, we show that LSD reorganizes brain networks by enhancing high-frequency alpha and beta rhythms while suppressing lower-frequency counterparts. These changes occur across various experimental conditions and shift the spatial distribution of brain activity, particularly in motor and visual regions. Our findings suggest that LSD modulates brain connectivity in a frequency- and region-specific manner, offering new insights into how psychedelics alter consciousness. This work advances our understanding of LSDs neural effects, which may be relevant for therapeutic applications and models of brain function.

neuroscience↗

bioRxiv2025

Structural Determinants of Signal Speed: A Multimodal Investigation of Face Processing in Autism Spectrum Disorder

It has not previously been possible to investigate the fundamental relationship between axonal structure - which dictates action potential transmission - and human neuronal function in vivo. Here, we introduce a novel metric of axonal signal speed, estimated axonal latency (EAL), derived from the relationship between axonal diameter, myelination, and length measured via MRI. We validate EAL along two pathways of the face processing network by relating it to N170 latency, an electrophysiological marker of face processing speed measured via EEG. Our results show that EAL along these pathways predicts N170 latency specifically during face processing. Moreover, we demonstrate that individuals with and without autism rely upon different pathways, potentially providing a structural account for autism-related face processing differences. By establishing this relationship between EEG-based electrical function and MRI-based axonal microstructure, we provide a non-invasive, spatially detailed estimate of neuronal processing speed that can inform our understanding of brain function, development, and disorder. TeaserEstimated axonal latency is a non-invasive, spatially detailed measure of neuronal speed to inform brain function and disorder.

neuroscience↗

bioRxiv2024

The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State

Lysergic acid diethylamide (LSD) is a classic serotonergic psychedelic that induces a profoundly altered conscious state. In conjunction with psychological support, it is currently being explored as a treatment for generalized anxiety disorder and depression. The dorsolateral prefrontal cortex (DLPFC) is a brain region that is known to be involved in mood regulation and disorders; hypofunction in the left DLPFC is associated with depression. This study investigated the role of the DLPFC in the psycho-emotional effects of LSD with functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) data of healthy human participants during the acute LSD experience. In the fMRI data, we measured the correlation between changes in resting-state functional connectivity (RSFC) of the DLPFC and post-scan subjective ratings of positive mood, emotional arousal, and ego dissolution. We found significant, positive correlations between ego dissolution and functional connectivity between the left & right DLPFC, thalamus, and a higher-order visual area, the fusiform face area (FFA). Additionally, emotional arousal was significantly associated with increased connectivity between the right DLPFC, intraparietal sulcus (IPS), and the salience network (SN). A confirmational "reverse" analysis, in which the outputs of the original RSFC analysis were used as input seeds, substantiated the role of the right DLPFC and the aforementioned regions in both ego dissolution and emotional arousal. Subsequently, we measured the effects of LSD on directed functional connectivity in MEG data that was source-localized to the input and output regions of both the original and reverse analyses. The Granger causality (GC) analysis revealed that LSD increased information flow between two nodes of the ego dissolution network, the thalamus and the DLPFC, in the theta band, substantiating the hypothesis that disruptions in thalamic gating underlie the experience of ego dissolution. Overall, this multimodal study elucidates a role for the DLPFC in LSD-induced states of consciousness and sheds more light on the brain basis of ego dissolution.

neuroscience↗

bioRxiv2024

Natural Variation in Age-Related Dopamine Neuron Degeneration is Glutathione-Dependent and Linked to Life Span

Aging is the biggest risk factor for Parkinsons disease (PD), suggesting that age-related changes in the brain promote dopamine neuron vulnerability. It is unclear, however, whether aging alone is sufficient to cause significant dopamine neuron loss and if so, how this intersects with PD-related neurodegeneration. Here, through examining a large collection of naturally varying Drosophila strains, we find a strong relationship between life span and age-related dopamine neuron loss. Strains with naturally short-lived animals exhibit a loss of dopamine neurons but not generalized neurodegeneration, while animals from long-lived strains retain dopamine neurons across age. Metabolomic profiling reveals lower glutathione levels in short-lived strains which is associated with elevated levels of reactive oxygen species (ROS), sensitivity to oxidative stress and vulnerability to silencing the familial PD gene parkin. Strikingly, boosting neuronal glutathione levels via glutamate-cysteine ligase (Gcl) overexpression is sufficient to normalize ROS levels, extend life span and block dopamine neurons loss in short-lived backgrounds, demonstrating that glutathione deficiencies are central to neurodegenerative phenotypes associated with short longevity. These findings may be relevant to human PD pathogenesis, where glutathione depletion is reported to occur in idiopathic PD patient brain through unknown mechanisms. Building on this, we find reduced expression of the Gcl catalytic subunit in both Drosophila strains vulnerable to age-related dopamine neuron loss and in human brain from familial PD patients harboring the common LRRK2 G2019S mutation. Our study across Drosophila and human PD systems suggests that glutathione synthesis and levels play a conserved role in regulating age-related dopamine neuron health.

neuroscience↗