Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anesthetized states induced by ketamine

Li, Duan; Vlisides, Phillip E.; Mashour, George A.

doi:10.1016/j.neuroimage.2022.118891

Cited by 7 publications

(8 citation statements)

References 90 publications

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“…Moreover, certain functional alterations may only occur at specific frequencies, underlining the importance of evaluating the connectome at different bands ( Sasai et al, 2021 ). While not specifically developed for FC, the investigation of frequency-specific functional alterations has been shown to offer additional insight into pharmacological mechanisms, including those triggered by S-ketamine ( Duan et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Functional ultrasound detects frequency-specific acute and delayed S-ketamine effects in the healthy mouse brain

2023

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IntroductionS-ketamine has received great interest due to both its antidepressant effects and its potential to induce psychosis when administered subchronically. However, no studies have investigated both its acute and delayed effects using in vivo small-animal imaging. Recently, functional ultrasound (fUS) has emerged as a powerful alternative to functional magnetic resonance imaging (fMRI), outperforming it in sensitivity and in spatiotemporal resolution. In this study, we employed fUS to thoroughly characterize acute and delayed S-ketamine effects on functional connectivity (FC) within the same cohort at slow frequency bands ranging from 0.01 to 1.25 Hz, previously reported to exhibit FC.MethodsWe acquired fUS in a total of 16 healthy C57/Bl6 mice split in two cohorts (n = 8 received saline, n = 8 S-ketamine). One day after the first scans, performed at rest, the mice received the first dose of S-ketamine during the second measurement, followed by four further doses administered every 2 days. First, we assessed FC reproducibility and reliability at baseline in six frequency bands. Then, we investigated the acute and delayed effects at day 1 after the first dose and at day 9, 1 day after the last dose, for all bands, resulting in a total of four fUS measurements for every mouse.ResultsWe found reproducible (r > 0.9) and reliable (r > 0.9) group-average readouts in all frequency bands, only the 0.01–0.27 Hz band performing slightly worse. Acutely, S-ketamine induced strong FC increases in five of the six bands, peaking in the 0.073–0.2 Hz band. These increases comprised both cortical and subcortical brain areas, yet were of a transient nature, FC almost returning to baseline levels towards the end of the scan. Intriguingly, we observed robust corticostriatal FC decreases in the fastest band acquired (0.75 Hz–1.25 Hz). These changes persisted to a weaker extent after 1 day and at this timepoint they were accompanied by decreases in the other five bands as well. After 9 days, the decreases in the 0.75–1.25 Hz band were maintained, however no changes between cohorts could be detected in any other bands.DiscussionIn summary, the study reports that acute and delayed ketamine effects in mice are not only dissimilar but have different directionalities in most frequency bands. The complementary readouts of the employed frequency bands recommend the use of fUS for frequency-specific investigation of pharmacological effects on FC.

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Section: Introductionmentioning

confidence: 99%

Functional ultrasound detects frequency-specific acute and delayed S-ketamine effects in the healthy mouse brain

2023

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“…wakefulness (Farnes et al, 2020;Li & Mashour, 2019). Another study confirmed these results, showing that ketamine deep sedation was found to show dynamic shifts in the organisation of brain states, transitioning from a diminished repertoire richness to a level comparable to that observed during normal wakefulness right before recovery (Li et al, 2022). This is consistent with a disruption of connected consciousness during ketamine deep sedation, marked by vivid experiences that are disconnected from the environment (e.g., dreams, hallucinations), alongside a complete unawareness of environmental events (Grace, 2003).…”

Section: Discussionmentioning

confidence: 60%

Ketamine-Induced Unresponsiveness Shows a Harmonic Shift from Global to Localised Functional Organisation

Van Maldegem,

Vohryzek,

Atasoy

et al. 2024

Preprint

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Ketamine is classified as a dissociative anaesthetic that, in sub-anaesthetic doses, can produce an altered state of consciousness characterised by dissociative symptoms, visual and auditory hallucinations, and perceptual distortions. Given the anaesthetic-like and psychedelic-like nature of this compound, it is expected to have different effects on brain dynamics in anaesthetic doses than in low, sub-anaesthetic doses. We investigated this question using connectome harmonic decomposition (CHD), a recently developed method to decompose brain activity in terms of the network organisation of the underlying human structural connectome. Previous research using this method has revealed connectome harmonic signatures of consciousness and responsiveness, with increased influence of global network structure in disorders of consciousness and propofol-induced sedation, and increased influence of localised patterns under the influence of classic psychedelics and sub-anaesthetic doses of ketamine, as compared to normal wakefulness. When we applied the CHD analytical framework to resting-state fMRI data of volunteers during ketamine-induced unresponsiveness, we found increased prevalence of localised harmonics, reminiscent of altered states of consciousness. This is different from traditional GABAergic sedation, where instead the prevalence of global rather than localised harmonics seems to increase with higher doses. In addition, we found that ketamine’s harmonic signature shows higher alignment with those seen in LSD- or psilocybin-induced psychedelic states than those seen in unconscious individuals, whether due to propofol sedation or brain injury. Together, the results indicate that ketamine-induced unresponsiveness, which does not necessarily suppress conscious experience, seems to influence the prevalence of connectome harmonics in the opposite way compared to GABAergic hypnotics. We conclude that the CHD framework offers the possibility to track alterations in conscious awareness (e.g., dreams, sensations) rather than behavioural responsiveness – a discovery made possible by ketamine’s unique property of decoupling these two facets.

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“…Traditionally, ketamine is administered in a dose of 1–4.5 mg/kg intravenously or 6.5–13 mg/kg intramuscularly to induce anesthetic effects in humans, depending on the patient's age and the desired clinical effects 34,42 . Ketamine can disrupt frontal–parietal communication and induce anesthetic effects 43–46 . Ketamine also affects the cardiovascular system by acting on the sympathetic nervous system.…”

Section: The Anesthetic Effects Of Ketaminementioning

confidence: 99%

“… 34 , 42 Ketamine can disrupt frontal–parietal communication and induce anesthetic effects. 43 , 44 , 45 , 46 Ketamine also affects the cardiovascular system by acting on the sympathetic nervous system. The anesthetic effects of ketamine are dose‐dependent.…”

Section: The Anesthetic Effects Of Ketaminementioning

confidence: 99%

The role of NMDARs in the anesthetic and antidepressant effects of ketamine

Zhou,

Duan

2023

CNS Neurosci Ther

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BackgroundAs a phencyclidine (PCP) analog, ketamine can generate rapid‐onset and substantial anesthetic effects. Contrary to traditional anesthetics, ketamine is a dissociative anesthetic and can induce loss of consciousness in patients. Recently, the subanaesthetic dose of ketamine was found to produce rapid‐onset and lasting antidepressant effects.AimHowever, how different concentrations of ketamine can induce diverse actions remains unclear. Furthermore, the molecular mechanisms underlying the NMDAR‐mediated anesthetic and antidepressant effects of ketamine are not fully understood.MethodIn this review, we have introduced ketamine and its metabolism, summarized recent advances in the molecular mechanisms underlying NMDAR inhibition in the anesthetic and antidepressant effects of ketamine, explored the possible functions of NMDAR subunits in the effects of ketamine, and discussed the future directions of ketamine‐based anesthetic and antidepressant drugs.ResultBoth the anesthetic and antidepressant effects of ketamine were thought to be mediated by N‐methyl‐D‐aspartate receptor (NMDAR) inhibition.ConclusionThe roles of NMDARs have been extensively studied in the anaesthetic effects of ketamine. However, the roles of NMDARs in antidepressant effects of ketamine are complicated and controversial.

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Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anesthetized states induced by ketamine

Cited by 7 publications

References 90 publications

Functional ultrasound detects frequency-specific acute and delayed S-ketamine effects in the healthy mouse brain

Functional ultrasound detects frequency-specific acute and delayed S-ketamine effects in the healthy mouse brain

Ketamine-Induced Unresponsiveness Shows a Harmonic Shift from Global to Localised Functional Organisation

The role of NMDARs in the anesthetic and antidepressant effects of ketamine

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