Causal evidence for cholinergic stabilization of attractor landscape dynamics

Taylor, Natasha L.; Whyte, Christopher J.; Munn, Brandon R.; Chang, Catie; Lizier, Joseph T.; Leopold, David A.; Turchi, Janita N.; Zaborszky, Laszlo; Műller, Eli J.; Shine, James M.

doi:10.1016/j.celrep.2024.114359

Cell Reports

2024

DOI: 10.1016/j.celrep.2024.114359

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Causal evidence for cholinergic stabilization of attractor landscape dynamics

Natasha L. Taylor,

Christopher J. Whyte,

Brandon R. Munn

et al.

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2024

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Cited by 2 publications

References 65 publications

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Complex slow waves radically reorganise human brain dynamics under 5-MeO-DMT

Blackburne,

McAlpine,

Fabus

et al. 2024

Preprint

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5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a psychedelic drug known for its uniquely profound effects on subjective experience, reliably eradicating the perception of time, space, and the self. However, little is known about how this drug alters large-scale brain activity. We collected naturalistic electroencephalography (EEG) data of 29 healthy individuals before and after inhaling a high dose (12mg) of vaporised synthetic 5-MeO-DMT. We replicate work from rodents showing amplified low-frequency oscillations, but extend these findings with novel tools for characterising the organisation and dynamics of complex low-frequency spatiotemporal fields of neural activity. We find that 5-MeO-DMT radically reorganises low-frequency flows of neural activity, causing them to become incoherent, heterogeneous, viscous, fleeting, nonrecurring, and to cease their typical travelling forwards and backwards across the cortex compared to resting state. Further, we find a consequence of this reorganisation in broadband activity, which exhibits slower, more stable, low-dimensional behaviour, with increased energy barriers to rapid global shifts. These findings provide the first detailed empirical account of how 5-MeO-DMT sculpts human brain dynamics, revealing a novel set of cortical slow wave behaviours, with significant implications for extant neuroscientific models of serotonergic psychedelics.

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Complex slow waves radically reorganise human brain dynamics under 5-MeO-DMT

Blackburne,

McAlpine,

Fabus

et al. 2024

Preprint

View full text Add to dashboard Cite

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Altered basal forebrain regulation of intrinsic brain networks in depressive and anxiety disorders

Jamieson,

Steward,

Davey

et al. 2024

Preprint

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Altered connectivity both within and between the default mode and salience networks have been observed across depressive and anxiety disorders. Recent work has highlighted the importance of subcortical regions, including subdivisions of the basal forebrain, in coordinating activity of these networking. However, the influence of specific basal forebrain subregions on intrinsic networks across these disorders remains unknown. Using ultra-high field (7-Tesla) functional magnetic resonance imaging, we examined the resting-state effective connectivity of three basal forebrain subregions in a transdiagnostic group of 70 individuals with depressive and anxiety disorders compared to 78 healthy controls. We explored connectivity between these subregions and regions of the salience network (anterior insula and dorsal anterior cingulate) and default mode network (ventromedial prefrontal cortex, posterior cingulate cortex, and inferior parietal lobule). Clinical participants showed increased inhibitory connectivity from the nucleus basalis of Meynert to regions of the default mode network and dorsal anterior cingulate. Increased inhibitory connectivity was also observed from the ventral pallidum to regions of the posterior default mode network. These changes in the basal forebrain's regulation of large-scale cortical networks across depressive and anxiety disorders may suggest novel mechanistic avenues for pharmacological treatments, including cholinergic system targeting.

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Causal evidence for cholinergic stabilization of attractor landscape dynamics

Cited by 2 publications

References 65 publications

Complex slow waves radically reorganise human brain dynamics under 5-MeO-DMT

Complex slow waves radically reorganise human brain dynamics under 5-MeO-DMT

Altered basal forebrain regulation of intrinsic brain networks in depressive and anxiety disorders

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