Acute lysergic acid diethylamide induces a time-dependent shift toward hippocampal control of default mode network reorganization
Fahd François Hilal, Rayane Benkeddada, Jeanblanc Jérôme, Marion Sourty, Fall Sidy, Rachel Utama, Sima Soltanpour, Praveen P Kulkarni, Mickaël Naassïla, Sami Ben Hamida, Md Taufiq Nasseef
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Sample size | 9 |
| Population | Male Long-Evans rats |
| Intervention | LSD |
| Dose | 500 μg/kg, i.p. |
| Duration | 15-min baseline, two consecutive 15-min post-injection periods |
| Topics | Default mode network LSD |
| Key findings | Acute LSD induced time-dependent changes in brain connectivity: early increases in functional coupling and reduced directed cortical interactions (retrosplenial-to-infralimbic influence), followed by later decreases and greater hippocampal involvement, suggesting a shift toward hippocampal-centered network control. |
Abstract
Background: Classical psychedelics induce profound changes in brain function, yet the temporal organization of these effects remains incompletely understood.
Methods: We investigated the effects of acute lysergic acid diethylamide (LSD) on large-scale brain connectivity in nine male Long–Evans rats using resting-state functional magnetic resonance imaging. Following a 15-min baseline acquisition, rats received LSD (500 μg/kg, i.p.), and imaging continued during two consecutive 15-min post-injection periods. Network reorganization was assessed using independent component analysis (ICA), seed-to-voxel mapping, stationary seed-to-seed connectivity, dynamic graph-based metrics, and dynamic causal modeling.
Results: LSD produced widespread but regionally heterogeneous changes across default mode network related, cortical, striatal, thalamic, sensory, and limbic systems. During the early post-injection window, ICA revealed a predominance of increased functional coupling, while dynamic analyses showed prominent fluctuations in hippocampal coupling strength and medial frontal network centrality. Dynamic causal modeling identified a false discovery rate–corrected reduction in retrosplenial-to-infralimbic influence, accompanied by a broader descriptive pattern of reduced posterior- and hippocampal-to-frontal coupling. During the later window, ICA showed a relative shift toward connectivity decreases, while complementary analyses revealed more selective hippocampal and parahippocampal involvement.
Conclusions: Across complementary analyses, acute LSD induced a temporally structured reorganization of brain hierarchy, characterized by an early weakening of directed cortical interactions followed by a later shift toward hippocampal-centered network control. These findings identify a dynamic shift in effective network organization and provide a mechanistic framework for psychedelic-induced default mode network reconfiguration.
Comparable studies
Other preclinical and animal studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rat brains also have a default mode network Rats | 2012 | Observational study | |
| Large-scale topology and the default mode network in the mouse connectome Mouse brain | 2014 | Observational study | |
| Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network Anesthetized monkeys | 2016 | Observational study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Altered functional connectivity within the default mode network in two animal models with opposing episodic memories Rats (control, LPS-challenged, and footshock-exposed groups) | 2018 | Animal model study |