Serotonergic psychedelics delay resting state neurovascular coupling dynamics
Lautaro Mundel, Vicente Medel, Christopher Timmermann, Patricio Orio, Josephine Cruzat, Carla Pallavicini, Gustavo Deco, Agustin Ibanez, Robin Carhart-Harris, Yonatan Sanz Perl, Enzo Tagliazucchi
Study at a glance
AI-extracted from the abstract| Characteristics | Observational neuroimaging study |
|---|---|
| Interventions | LSD DMT |
| Measures | BOLD signal, blind deconvolution algorithm, whole-brain functional connectivity, biophysical whole-brain model |
| Topics | Serotonin |
| Key findings | LSD and DMT increased estimated hemodynamic delays in regions overlapping serotonin receptor distribution implicated in psychedelic action and vascular regulation. Deconvolution enhanced detection of psychedelic-induced whole-brain functional connectivity changes, indicating vascular effects obscure connectivity changes rather than generate spurious results. A biophysical model linked these effects to increased flow-dependent feedback and slower dissipation of vasoactive drive. |
Abstract
Psychedelics are increasingly explored as tools to investigate consciousness and cognition, and as potential treatments for mood disorders. While neuroimaging has been central to characterizing their mechanisms of action, the interpretation of these studies may be confounded by the neurovascular effects elicited by these drugs. Here, we investigated the modulation of resting state neurovascular coupling by the serotonergic psychedelics LSD and DMT. Applying a blind deconvolution algorithm to blood-oxygen-level-dependent (BOLD) signals, we found that both drugs increased the estimated hemodynamic delays in regions overlapping with the distribution of serotonin receptors implicated in psychedelic action and vascular regulation. Deconvolution enhanced the detection of psychedelic-induced changes in whole-brain functional connectivity, suggesting that vascular effects obscure connectivity changes instead of generating spurious results. Finally, a biophysical whole-brain model linked these effects to increased flow-dependent feedback and slower dissipation of the vasoactive drive. These findings underscore the need to account for vascular effects in future psychedelic neuroimaging studies.
Comparable studies
Other experimental studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Rat brain | 1997 | Experimental study |