From hallucinations to synaesthesia: A circular inference account of unimodal and multimodal erroneous percepts in clinical and drug-induced psychosis

Leptourgos, Pantelis; Bouttier, Vincent; Jardri, Renaud

doi:10.1016/j.neubiorev.2022.104593

Cited by 9 publications

(11 citation statements)

References 110 publications

(149 reference statements)

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“…Furthermore, they expand upon previous studies that have found that early sensory activity can lead to false alarms [26][27][28][29][30]43 , by suggesting that the activity reported by these studies may reflect spontaneous fluctuations in the input layers, rather than feedback from higher-order regions. Recent circular inference models of hallucinations have emphasised the role of ascending loops, akin to feedforward activity, in unimodal hallucinations as seen in psychotic disorders 20,44 . Specifically, they suggest that weak sensory signals can trigger perceptual hypotheses that are then counted as sensory evidence themselves in runaway 'overcounting' loops.…”

Section: Discussionmentioning

confidence: 99%

Perceptual expectations and false percepts generate stimulus-specific activity in distinct layers of the early visual cortex

Haarsma

Deveci

Corbin

et al. 2022

Preprint

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Popular theories suggest that hallucinations arise through excessive top-down perceptual expectations, whereas others have emphasised the role of spontaneous bottom-up activity. These theories make different predictions about how input and feedback layers in sensory regions contribute to hallucinations. Here, we used layer-specific fMRI to interrogate neural activity underlying hallucinations - high confidence false percepts - and perceptual expectations while healthy participants (N=25) performed a perceptual discrimination task. We found that false percepts were related to stimulus-like activity in the middle input layers of V2. On the other hand, perceptual expectations activated the deep feedback layers of V2, without influencing perception. The prevalence of high confidence false percepts was related to everyday hallucination severity, confirming their ecological validity. These results reveal that hallucinations can arise through spontaneous stimulus-specific activity in the input layers of the visual cortex, independent of top-down perceptual expectations.

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Section: Discussionmentioning

confidence: 99%

Perceptual expectations and false percepts generate stimulus-specific activity in distinct layers of the early visual cortex

Haarsma

Deveci

Corbin

et al. 2022

Preprint

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show abstract

“…Our results along with preclinical studies [42,46,47] and recent magnetic resonance spectroscopy results [44] suggest that LSD may perturb the E/I balance of the brain. This is especially relevant because disturbances in the E/I balance have been discussed in the context of psychosis [48,49] and more recently in the context of psychedelic-induced hallucinations and synaesthesia [50]. Comparing LSD-induced changes in E/I balance to other psychedelics and those associated with clinical psychosis will be an interesting avenue for future research.…”

Section: Does Lsd Perturb the Excitation/inhibition (E/i) Balance?mentioning

confidence: 99%

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Bedford

Hauke

Wang

et al. 2023

Neuropsychopharmacol.

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Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future.

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“…Because rDCM summarises region-specific E/I balance by a single parameter per region, we cannot determine whether excitation, inhibition, or both are impacted. Future studies should employ more detailed models that allow to pinpoint these changes and compare them empirically to 15 other conditions in which the E/I balance is affected, for example psychosis (Jardri et al, 2017;Leptourgos et al, 2022).…”

Section: Future Directionsmentioning

confidence: 99%

“…Our results along with preclinical studies (Aghajanian and Marek, 1999;Scruggs et al, 2000Scruggs et al, , 2003 and recent magnetic resonance spectroscopy results (Mason et al, 2020) suggest that LSD may perturb the E/I balance of the brain. This is especially relevant because disturbances in the E/I balance have been discussed in the context of psychosis (Jardri and Deneve, 2013;Jardri et al, 2017) and more recently in the context of psychedelic-induced hallucinations and synaesthesia (Leptourgos et al, 2022). Comparing LSD-induced changes in E/I balance to other psychedelics and those associated with clinical psychosis will be an interesting avenue for future research.…”

Section: Does Lsd Perturb the Excitation/inhibition (E/i) Balance?mentioning

confidence: 99%

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Bedford

Hauke

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomized, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed widespread increases in interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of primarily decreased interregional connectivity and increased self-inhibition in occipital brain regions. This finding suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Moreover, random forests classified LSD vs. placebo states based on FC and EC with comparably high accuracy (FC: 85.56%, EC: 91.11%) suggesting that both EC and FC are promising candidates for clinically-relevant biomarkers of LSD effects.

show abstract

From hallucinations to synaesthesia: A circular inference account of unimodal and multimodal erroneous percepts in clinical and drug-induced psychosis

Cited by 9 publications

References 110 publications

Perceptual expectations and false percepts generate stimulus-specific activity in distinct layers of the early visual cortex

Perceptual expectations and false percepts generate stimulus-specific activity in distinct layers of the early visual cortex

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

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