Acute lysergic acid diethylamide induces a time-dependent shift toward hippocampal control of default mode network reorganization
- 1Prince Sattam Bin Abdulaziz University
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 g/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.
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BibTeX
@misc{hilal2026acute,
title = {{Acute lysergic acid diethylamide induces a time-dependent shift toward hippocampal control of default mode network reorganization}},
author = {F. F. Hilal and R. Benkeddada and J. Jerome and M. Sourty and F. Sidy and R. Utama and S. Soltanpour and P. Kulkarni and M. Naassila and S. Ben Hamida and M. T. Nasseef},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.748807},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.748807v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Acute lysergic acid diethylamide induces a time-dependent shift toward hippocampal control of default mode network reorganization
AU - F. F. Hilal
AU - R. Benkeddada
AU - J. Jerome
AU - M. Sourty
AU - F. Sidy
AU - R. Utama
AU - S. Soltanpour
AU - P. Kulkarni
AU - M. Naassila
AU - S. Ben Hamida
AU - M. T. Nasseef
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.748807
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.748807v1
AB - 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 g/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.
ER -