DMT increases forward (bottom‑up) cortical travelling waves and suppresses top‑down alpha rhythms, producing spatio‑temporal activation similar to visual stimulation despite eyes being closed. These effects support a predictive‑processing account in which psychedelics reduce the precision‑weighting of priors, shifting the balance toward bottom‑up signalling.
Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the ‘precision-weighting of priors’, thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.
N,N-Dimethyltryptamine (DMT) is a serotonergic psychedelic that produces a rapid, short-lived but intensely immersive visual and perceptual state. Earlier EEG and MEG studies of ayahuasca and of intravenously administered DMT have consistently reported broadband decreases in oscillatory power—particularly in the alpha band (8–12 Hz)—and increases in signal diversity; decreases in alpha power have correlated with the intensity of visual phenomenology. Separately, non-drug studies have described spatio-temporal patterns of cortical activity known as travelling waves: forward (occipital-to-frontal) waves predominate during visual perception, whereas backward (frontal-to-occipital) waves predominate during eyes-closed rest. These travelling waves have been linked to predictive-coding accounts in which direction of propagation relates to bottom-up prediction errors and top-down predictions respectively. Alamia and colleagues set out to test whether DMT alters the amount and direction of cortical travelling waves during eyes-closed resting conditions, and whether any such changes relate to the vivid visual imagery produced by the drug. The primary hypothesis was that DMT would disrupt the physiological balance between top-down and bottom-up information flow in favour of increased bottom-up signalling, manifesting as decreased backward waves and increased forward waves similar to those observed during actual visual stimulation. The study therefore aimed to quantify travelling-wave directionality and frequency under placebo versus intravenously administered DMT and to relate these measures to real-time and post-hoc subjective reports of intensity and visual imagery.
Papers cited by this study that are also in Blossom
Timmermann, C., Roseman, L., Schartner, M. et al. · Scientific Reports (2019)
Riba, J., Anderer, P., Morte, A. et al. · British Journal of Clinical Pharmacology (2002)
Schenberg, E. E., Alexandre, J. F. M., Filev, R. et al. · PLOS ONE (2015)
Valle, M., Maqueda, A. E., Rabella, M. et al. · European Neuropsychopharmacology (2016)
This analysis reused a previously collected dataset. Thirteen healthy participants (6 female; the extracted text does not clearly report mean age) completed two sessions: a placebo session and a DMT session. DMT was administered intravenously in ascending doses across participants (reported doses: 7 mg to 20 mg, distributed across participants as 7 mg to 3 participants, 14 mg to 4 participants, 18 mg to 1 participant, and 20 mg to 5 participants). Participants were medically and psychiatrically screened; standard exclusion criteria (age under 18, no prior psychedelic experience, history of psychiatric illness, excessive alcohol use) and pre-session drug/pregnancy/breathalyser checks were applied. During each session participants rested semi-supine with eyes closed; eye closure was monitored visually. EEG was recorded with a 32-channel BrainProducts system at 1,000 Hz. Signals were filtered (high-pass 0.1 Hz, anti-aliasing low-pass 450 Hz, band-pass 1–45 Hz), epochs with artefacts removed visually, and ICA used to remove ocular and cardiac components. Data were re-referenced to the average of electrodes. Travelling-wave quantification used a sliding 1-second window with 0.5-second overlap. For each window the authors formed a time–electrode 2D map from five midline electrodes (Oz, POz, Pz, Cz, FCz) and computed a 2D Fast Fourier Transform (2D-FFT). The maximum values in the upper and lower quadrants of the 2D-FFT were taken as raw measures of forward (FW) and backward (BW) wave power respectively. To obtain a null distribution that preserves temporal spectral content but destroys spatial directionality, electrode order was shuffled 100 times and the surrogate FW and BW values averaged. The net amount of FW and BW waves was then expressed in decibels (dB) as the log-ratio of true to surrogate values; this metric indexes the amount of wave power beyond that expected from temporal fluctuations alone and can be tested against zero to assess significance. Frequencies of maximal peaks from the 2D-FFT were analysed to assess band-specific changes. Statistical analyses comprised separate Bayesian ANOVAs for FW and BW measures with factors pre/post injection and drug (DMT versus placebo), treating subjects as random factors. Minute-by-minute analyses used t-tests at each time bin against zero with False Discovery Rate (FDR) correction. Correlations were computed between minute-by-minute intensity ratings (collected every minute for 20 minutes post-injection) and wave amplitudes, and between post-session visual imagery questionnaire items (Visual Analogue Scale) and wave measures. The authors note a reduced number of datapoints (n=12) for some correlational analyses as reported in the extracted text.
Baseline (pre-injection) closed-eyes recordings showed a significant predominance of backward travelling waves in both placebo and DMT sessions (Bayesian t-tests against zero: BFs10 >> 100), with no significant forward waves (BFs10 < 0.15). After intravenous DMT, the cortical dynamics changed: backward wave amplitude decreased relative to baseline but remained above zero (BFs10 = 12.6), while forward wave amplitude increased significantly above zero (BF10 = 5.4). These pre/post by drug effects were supported by separate Bayesian ANOVAs run for FW and BW measures (reported BFs10 >> 100 for factors and interactions). A minute-by-minute analysis showed that changes emerged rapidly after injection and decayed over the subsequent tens of minutes. Forward waves increased and backward waves decreased during the peak DMT effect period; the time-bin tests against zero survived FDR correction in several minutes for FW and consistently for BW (all FDR-corrected p-values < 0.05 where reported). When compared qualitatively with results from a separate experiment involving alternating visual stimulation and blank-screen periods, the temporal profiles of FW and BW changes under DMT were remarkably similar to those observed during photic visual stimulation, despite participants having their eyes closed under DMT. Examining spectral content, both FW and BW wave spectra showed a strong alpha-band presence at baseline. Following DMT, alpha-band power associated with these waves decreased markedly while delta (0.5–4 Hz) and theta (4–7 Hz) bands increased for both wave directions (all BFs10 > 100). Absolute spectral power from the 2D-FFT also decreased in the alpha band after DMT, a pattern akin to that seen with visual stimulation. Analyses of FW–BW relationships during the interval when both were significantly present (minutes 2–5 post-DMT) revealed a robust negative correlation between their net amounts on a moment-by-moment basis: FW tended to be weaker when BW was stronger and vice versa. This inverse relationship was consistent across participants and appeared independent of drug condition (difference between pre and post, Bayesian t-test BF10 = 0.225). Relating waves to subjective experience, minute-by-minute intensity ratings correlated positively with forward-wave amplitude and negatively with backward-wave amplitude; these time-resolved correlations peaked a few minutes after injection. Across participants, correlations between intensity ratings and wave amounts reached coefficients of approximately 0.4 around peak effect but did not achieve statistical significance after correction, a shortfall the authors attribute to limited sample size (n=12 for some analyses). Post-session visual imagery ratings (Visual Analogue Scale) showed a consistent positive relationship with the amount of forward waves across all 20 questionnaire items; Bayesian tests indicated strong evidence for FW associations (BFs >> 100) and no evidence for BW associations (BF = 0.41).
Alamia and colleagues interpret their findings as evidence that intravenous DMT shifts cortical spatio-temporal dynamics away from the typical eyes-closed dominance of backward travelling waves toward increased forward propagation, producing a pattern closely resembling that seen during genuine visual stimulation. They report concurrent decreases in alpha-band oscillatory power and increases in slower bands, and note that increases in forward-wave amplitude correlated with both real-time intensity ratings and post-hoc visual imagery measures. Taken together, the authors argue these observations link cortical travelling-wave directionality with conscious visual phenomenology: forward waves in particular appear to map onto vivid visual experience whether driven by external stimulation or DMT-induced endogenous imagery. Placing the results in the broader literature, the authors reference prior neuroimaging work showing occipital activation during ayahuasca imagery and earlier EEG findings of reduced alpha and increased signal diversity under psychedelics, reasoning that their travelling-wave results dovetail with these observations. They further discuss pharmacological considerations, noting that classic psychedelics, including DMT, exert actions primarily via 5-HT2A receptor agonism; this receptor has been implicated in drug-induced hallucinations and in clinical hallucinations in neurological disorders, offering a plausible receptor-level mediator of the observed cortical effects. The discussion frames the findings in predictive-coding terms: if backward waves convey top-down predictions and forward waves convey bottom-up prediction errors, then a DMT-induced reduction in backward waves and increase in forward waves is consistent with models positing that psychedelics reduce the precision weighting of priors and thereby liberate bottom-up signalling. The authors suggest that their data provide mechanistic support for this account and propose that similar travelling-wave shifts might characterise other endogenous visionary states such as dreaming or non-drug hallucinations; they recommend future work to test this conjecture and to examine other sensory modalities. The authors acknowledge limitations in the correlational analyses due to limited statistical power (n=12 in some tests) and the indirect nature of certain comparisons (for example, the visual-stimulation data derive from a different experiment with different participants and EEG setups). They therefore present their conclusions as consistent with, but not definitive proof of, the proposed predictive-coding interpretation, and they call for further studies to generalise and extend the present findings.
These are reported as the first EEG data examining human resting-state brain activity under pure DMT. Consistent with the study hypothesis, DMT shifted cortical travelling waves away from the baseline predominance of backward waves toward increased forward waves—a pattern resembling eyes-open visual stimulation—while reducing alpha-band oscillations. Increases in forward-wave amplitude correlated with both the time-resolved intensity of the DMT experience and post-session measures of visual imagery. The authors conclude that these results have implications for understanding the neural mechanisms of the psychedelic state and for theories of conscious visual perception.
N,N, Dimethyltryptamine (DMT) is a mixed serotonin receptor agonist that occurs endogenously in several organismsincluding humans. DMT, which is a classic psychedelic drug, is also taken exogenously by humans to alter the quality of their consciousness. For example, synthesized compound is smoked or injected but it has also been used more traditionally in ceremonial contexts (e.g. in Amerindian rituals). When ingested orally, DMT is metabolized in the gastrointestinal (GI) system before reaching the brain. Its consumption has most traditionally occurred via drinking 'Ayahuasca', a brew composed of plant-based DMT and β -carbolines (monoamine oxidize inhibitors), which inhibit the GI breakdown of the DMT. Modern scientific research has mostly focused on intravenously injected DMT. Administered in this way, DMT's subjective effects have a rapid onset, reaching peak intensity after about 2-5 minutes and subsiding thereafter, with negligible effects felt after about 30 minutes. Previous electrophysiological studies investigating changes in spontaneous (resting state) brain function elicited by ayahuasca have reported consistent broadband decreases in oscillatory power, while others have noted that the most marked decreases occur in α-band oscillations (8-12 Hz). Alpha decreases correlated inversely with the intensity of ayahuasca-induced visual hallucinationsand are arguably the most reliable neurophysiological signature of the psychedelic state identified to-datewith increased signal diversity or entropy being another particularly reliable biomarker. In the first EEG study of the effects of pure DMT on on-going brain activity, marked decrease in the α and β (13 -30 Hz) band power were observed as well as increases in signal diversity. Increases in lower frequency band power (δ = 0.5 -4 Hz and θ = 4 -7 Hz) also became evident when the signal was decomposed into its oscillatory component. Decreased alpha power and increased signal diversity correlated most strongly with DMT's subjective effectsconsolidating the view that these are principal signatures of the DMT state, if not the psychedelic state more broadly. Focusing attention onto normal brain function, outside of the context of psychoactive drugs, electrophysiological recordings in cortical regions reveal distinct spatio-temporal dynamics during visual perception, which differ considerably from those observed during closed-eyes restfulness. It is possible to describe these dynamics as oscillatory 'travelling waves', i.e. fronts of rhythmic activity which propagate across regions in the cortical visual hierarchy. Recent results showed that travelling waves can spread from occipital to frontal regions during visual perception, reflecting the forward bottom-up flow of information from lower to higher regions. Conversely, top-down propagation from higher to lower regions appears to predominate during quiet restfulness. Taken together these results compel us to ask how travelling waves may be affected by DMT, particularly given their association with predictive codingand a recent predictive coding inspired hypothesis on the action of psychedelicswhich posits decreased top-down processing and increased bottom up signal passing under these compounds. Moreover, DMT lends itself particularly well to the testing of this hypothesis as its visual effects are so pronounced. Given that visual perception is associated with an increasing in forward travelling waves and eyes-closed visual imagery under DMT can feel as if one is 'seeing with eyes shut'does a consistent increase in forward travelling waves under DMT account for this phenomenon? Here we sought to address these questions by quantifying the amount and direction of travelling waves in a sample of healthy participants who received DMT intravenously, during eyes-closed conditions. We hypothesized that DMT acts by disrupting the normal physiological balance between top-down and bottom-up information flow, in favor of the latter. Moreover, does this effect correlate with the vivid 'visionary' component of the DMT experience? Providing evidence in favor of this hypothesis would indicate that forward travelling waves do play a crucial role in conscious visual experience, irrespective of the presence of actual photic stimulation.
Quantifying travelling waves. We measure the waves' amount and direction with a method devised in our previous studies. We slide a one-second time-window over the EEG signals (with 0.5s overlap). For each time window, we generate a 2D map (time/electrodes) by stacking the signals from 5 central mid-line electrodes (Oz to FCz, see figure). For each map, we then compute a 2D-FFT, in which the upper-and lower-left quadrant represent the power of forward (FW) and backward (BW) travelling waves, respectively (since the 2D-FFT is symmetrical around the origin, the lower-and upper-right quadrants contain the same information). From both quadrants we extracted the maximum values, representing the raw amount of FW and BW waves in that time-window. Next, we performed the same procedure after having shuffled the electrodes' order, thereby disrupting spatial information (including the waves' directionality) while retaining the same overall spectral power. In other words, the surrogate measures reflect the amount of waves expected solely due to the temporal fluctuations of the signal. After having computed the maximum values for the FW and BW waves of the surrogate 2D-FFT spectra one hundred times (and averaging the 100 values), we compute the net amount of FW and BW waves in decibel (dB), by applying the following formula: Importantly, this value -expressed in decibel-represents the net amount of waves against the null distribution. In other words, it is informative to compare this value to zero, to assess the significance of waves. On the other hand, a direct comparison between FW and BW waves in each time-bin is not readily interpretable, as it is possible to simultaneously record waves propagating in both directions-as observed during visual stimulation epochs (see below). Does DMT influence travelling waves? After defining our measure to assess the waves' amount and direction, we investigated whether the intake of DMT alters the cortical pattern of travelling waves. Participants underwent two sessions in which they were injected with either placebo or DMT (see Methods for details). Importantly, during all the experiments they rested in a semi-supine position, with their eyes closed. EEG recordings were collected 5 minutes prior to drugs administration and up to 20 minutes after. The left column of figureshows the amount of BW and FW waves in the 5 minutes preceding and following drug injection (either placebo or DMT). As previously reported, during quiet closed-eyes restfulness a significant amount of BW waves spread from higher to lower regions (as confirmed by a Bayesian t-test against zero for both DMT and Placebo conditions, BFs10>>100), whereas no significant waves propagate in the opposite FW direction (Bayesian t-test against zero: BFs10<0.15). However, after DMT injection the cortical pattern changed drastically: the amount of BW waves decreased (but remaining significantly above zero -BFs10=12.6) whereas the amount of FW waves increased significantly above zero (BF10=5.4). All in all, these results obtained by comparing the amount of waves before and after injection (pre-post factor) of Placebo or DMT (drug factor) were confirmed by two Bayesian ANOVA performed separately on BW and FW waves (all factors including interactions reported BFs10 >> 100). Additionally, we ran a more temporally precise analysis, on a minute by minute scale, testing the amount of FW and BW waves in the two conditions, as shown in the right panels of figure 2A. In line with previous studies, the changes in cortical dynamics appeared rapidly after intravenous DMT injection, and faded off within dozens of minutes. Confirming our previous analysis, we observed an increase in FW waves (asterisks in the lower right panel of figureshow FDR-corrected significant p-values when testing against zero) and a decrease in BW waves, which nonetheless remained above zero (all FDR-corrected p-values<0.05). To our initial surprise, the dynamics elicited by DMT injection were remarkably reminiscent of those observed in another study, in which healthy participants alternated visual stimulation with periods of blank screen, without any drug manipulation. Although a direct comparison is not statistically possible (because the two studies involved distinct subject groups and different EEG recording setups), we indirectly investigated the similarities between these two scenarios.
Comparison between the waves' temporal evolution after DMT injection (left panel) and with or without visual stimulation (right panel, from a different experiment in which participants, with open eyes, either watched a visual stimulus or a blank screen). Remarkably, the waves' temporal profiles are very similar in the two conditions, for both FW and BW. C) Comparison between changes in absolute power (as extracted from the 2D-FFT, i.e. FW and BW in figure) due to DMT, placebo and visual stimulation. Remarkably, true photic visual stimulation and eyes-closed DMT induce comparably large reductions in absolute power. In fact, the effect with DMT appears to be even more pronounced (formal contrast not appropriate). Note that in the previous panels the changes in the net amount of waves were reported in dB, and occurred irrespective of the global power changes measured in panel C. Comparison with perceptual stimulation. We recently showed that FW travelling waves increase during visual stimulation, whereas BW waves decrease, in line with their putative functional role in information transmission. In figure, for the sake of comparison, we contrast the cortical dynamics induced by DMT (left panel) with the results of our previous study (right panel), in which participants perceived a visual stimulus (label 'ON') or stared at a dark screen (label 'OFF'). Remarkably, mutatis mutandis, both FW and BW waves share a similar profile across the two conditions, increasing and decreasing respectively following DMT injection or visual stimulation. If we consider the absolute (maximum) power values derived from the 2D-FFT of each map (i.e., before estimating the surrogates and the waves' net amount in decibel) as an estimate of spectral power, we can read the results reported in figureas an overall decrease in oscillatory power following DMT injection, more specifically in the frequency band with the highest power values (i.e. alpha band, but see next paragraph). Such decrease in oscillatory power is also matched by a similar decrease induced by visual stimulation (all Bayesian t-test BFs10>>100). These results demonstrate that, despite participants having their eyes-closed throughout, DMT produces spatio-temporal dynamics similar to those elicited by true visual stimulation. These results therefore shed light on the neural mechanisms involved in DMT-induced visionary phenomena.
Previous studies showed that DMT alters specific frequency bands (e.g. alpha-band), mostly by decreasing overall oscillatory power. Here, we investigated whether DMT influences not only the waves' direction but also their frequency spectrum. We compared the frequencies of the maximum peaks extracted from the 2D-FFT (see figure) before and after DMT or Placebo injection. Before infusion, both FW and BW waves had a strong amount of waves oscillating in the alpha range (figure, left panel). Remarkably, following DMT injection, the waves' spectrum changed drastically, with a significant reduction in the alpha-band, coupled with an increase in the delta and theta bands, for both FW and BW waves (all BFs10>100). This result corroborates a previous analysis performed on EEG recordings from the same dataset 7 as well as independent data pertaining to O-Phosphoryl-4-hydroxy-N,N-DMT (psilocybin), a related compound. What's the relationship between FW and BW waves? From the left panel of figure, it seems that during the first minutes after DMT injection, both FW and BW waves are simultaneously present in the brain. In an attempt to understand the overall relationship between FW and BW waves, we focused on the minutes when both BW and FW waves were significantly larger than 0 (minutes 2 to 5 after DMT injection, see figure). On these data we performed a moment-by-moment correlation between their respective net amount (as measured in decibelsee figure). We found a clear and significant negative relationship, very consistent across participants and irrespective of DMT injection (difference between Pre and Post, Bayesian t-test BF10 = 0.225; figure, first panel). This result demonstrates that, in general, FW waves tend to be weaker whenever BW waves are stronger, and vice-versa. In other words, FW and BW remain present after drug injection, sum to a consistent total amount, and remain inversely related; it is only the ratio of contribution from each that changes after DMT (i.e. less BW, more FW waves). Is there a correlation between waves and subjective reports? We investigated whether changes in travelling waves under DMT correlated with the subjective effects of the drug. Specifically, for 20 minutes after DMT injection participants provided an intensity rating every minute and, when subjective effects faded, participants filled various questionnaires that addressed different aspects of the experience (see Timmermann et al., 2019 for details). First, we found a robust correlation between minute-by-minute intensity rates and the amplitude of the waves, as shown in the first panel of figure. This result reveals that the developing intensity of the drug's subjective effects and changes in the amplitude of waves correlate positively (FW) or negatively (BW) across time, both peaking a few minutes after drug injection. Second, treating each time point independently, we again correlated intensity ratings with the amount of each wave type, across subjects. The middle panel of figureshows a clear trend for the correlation coefficients over time. Despite the limited number of datapoints (n=12), the correlation coefficients reach high values (~0.4), implying that, around the moment where the drug had its maximal effect (2-5 minutes after injection), those subjects who reported the most intense effects were also those who had the strongest travelling waves in the FW direction, and the weakest waves in the BW direction. Finally, we correlated the amount of FW and BW waves with ratings focused specifically on visual imagery: remarkably, all the correlations between each questionnaire item correlated positively with the increased amount of FW waves under DMT. As the same relationship was not apparent for the BW waves, this consolidates the view that visionary experiences under DMT correspond to higher amounts of FW waves in particular. Taken together with previous results from visual stimulation experiments independent of DMT, these data strongly support the principle cortical travelling waves (and increased FW waves in particular) correlate with the conscious visual experiences, whether induced exogenously (via direct visual stimulation) or endogenously (visionary or hallucinatory experiences). Each dot represents a one-minute time-bin from DMT injection, the x-axis reflects the average intensity rating across subjects, and the y-axis indicates the average strength of BW or FW waves across subjects (both correlations p<0.0001). The middle panel shows the correlation coefficients across participants, obtained by correlating the intensity rates and the waves' amount separately for each time point. Solid lines show when the amount of waves is significantly larger than zero (always for BW waves, few minutes after DMT injections for FW waves -see figure). However, given the limited statistical power (N=12), and proper correction for multiple testing, correlations did not reach significance at any time point. The last panel shows the correlation coefficients between the visual imagery specific ratings provided at the end of the experiment (i.e. Visual Analogue Scale, see methods) and the net amount of waves (measured when both BW and FW were significantly different than zero, i.e. from minutes 2 to 5): for all 20 items in the questionnaire there was a positive trend between the amount of FW waves and the intensity of visual imagery, as confirmed by a Bayesian t-test against zero (BF for FW waves >> 100). We did not observe this effect in the BW waves (BF = 0.41).
In this study we investigated the effects of the classic psychedelic drug DMT on cortical spatio-temporal dynamics typically described as travelling waves. We analyzed EEG signals recorded from a pool of participants who kept their eyes closed while receiving drug. Results revealed that compared with consistent eyes-closed conditions under placebo, eyes-closed DMT is associated with striking changes in cortical dynamics, which are remarkably similar to those observed during actual eyesopen visual stimulation. Specifically, we observed a reduction in BW waves, and increase in FW ones, as well as an overall decrease in α band (8-12Hz) oscillatory frequencies. Moreover, increases in the amount of FW waves correlated positively with real-time ratings of the subjective intensity of the drug experience as well as posthoc ratings of visual imagery, suggesting a clear relationship between travelling waves and conscious experience.
Initiated by the discovery of mescaline, and catalyzed by the discovery of LSD, Western medicine has explored the scientific value and therapeutic potential of psychedelic compounds for over a century. DMT has been evoking particular interest in recent decades however, with new studies into its basic pharmacology, endogenous functionas well its effects on cortical activity in ratsand humans. There has been a surprising dearth of resting-state human neuroimaging studies of pure DMTwhich, given its profound and basic effects on conscious awareness, could be viewed as a scientific oversight. Previous work involving ayahuasca and BOLD fMRI found increased visual cortex BOLD signal under the drug vs placebo while participants engaged in an eyesclosed imagery task -a result that was interpreted as consistent with the 'visionary' effects of ayahuasca. Despite some initial debate, it is now generally accepted that occipital visual regions become activated during visual imagery. Placing these findings into the context of previous work demonstrating increased FW travelling waves during direct visual perception, our present findings of increased FW waves under DMT correlating with visionary experiences lend significant support to the notion that DMT/ayahuasca and perhaps other psychedelics, engage the visual apparatus in a fashion that is consistent with actual exogenously driven visual perception. Future work could extend this insight to other apparently endogenous generated visionary experiences such as occur during dreaming and hallucinatory states. We would hypothesize a consistent favoring of FW waves during these dates. If consistent mechanisms were also found to underpin hallucinatory experiences in other sensory modalitiessuch as the auditory one, a basic principle underlying sensory hallucinations might be established.
As a classic psychedelic drug, DMT's signature psychological effects are likely mediated by stimulation of the serotonin 2A (5-HT2A) receptor subtype. As with all other classic psychedelics 2 the 5-HT2A receptor has been found to be essential for the full signature psychological and brain effects of Ayahuasca. In addition to its role in mediating altered perceptual experiences under psychedelics, The 5-HT2A receptor has also been linked to visual hallucinations in neurological disorders, with a 5-HT2A receptor inverse agonist having been licensed for hallucinations and delusions in Parkinson's disease with additional evidence for its efficacy in reducing consistent symptoms in Alzheimer's disease. Until recently, a systems level mechanistic account of the role of 5-HT2A receptor agonism in visionary or hallucinatory experiences has however been lacking.
There is a wealth of evidence that predictive mechanisms play a fundamental role in cognitive and perceptual processingand our understanding of the functional architecture underlying such processing is continually being updated. According to predictive coding, the brain strives to be a model of its environment. More specifically, based on the assumption that the cortex is a hierarchical systemmessage passing from higher cortical levels is proposed to encode predictions about the activity of lower levels. This mechanism is interrupted when predictions are contradicted by the lower-level activity ('prediction error')in which case, information passes up the cortical hierarchy where it can update predictions. Predictive coding has recently served as a guiding framework for explaining the psychological and functional brain effects of psychedelic compounds. According to one model, psychedelics decrease the precision weighting of top-down priors, thereby liberating bottom-up information flow. Various aspects of the multi-level action of psychedelics are consistent with this model, such as the induction of asynchronous neuronal discharge rates in cortical layer 5, reduced alpha oscillationsincreased signal complexityand the breakdown of large-scale intrinsic networks. Recent empirically supported modelling work has lent support to the assumptions that top-down predictions and bottom-up prediction-errors are encoded in the direction of propagation of cortical travelling waves. This discovery opened-up a tantalizing opportunity for testing assumptions both about the nature of travelling waves and how they should be modulated by psychedelics. That prior assumptions were so emphatically endorsed by the data, including how propagation-shifts related to subjective experience, enables us to make strong inferences about both the functional relevance of cortical travelling waves and brain action of psychedelics. Future studies can now be performed to examine how these assumptions translate to other phenomena such as non-drug induce visionary and hallucinatory states.
These are the first EEG data on the effects of DMT on human resting state brain activity. In line with prior hypothesis, clear evidence was found of a shift in cortical travelling waves away from the normal basal predominance of backward waves and towards the predominance of forward waves -remarkably similar to what has been observed during eyes-open visual stimulation. Moreover, the increases in forward waves correlated positively with both the general intensity of DMT's subjective effects, as well as its more specific effects on eyes-closed visual imagery. These findings have specific and broad implications: for the brain mechanisms underlying the DMT/psychedelic state as well as conscious visual perception more broadly.
Participants and experimental procedure. In this study we analyzed a dataset presented in a previous publication, to address a very different scientific question using another analytical approach. Consequently, the information reported in this and the next paragraphs overlaps with the previous study (to which we refer the reader for additional details). Thirteen participants took part in this study (6 females, age 34. Participants were carefully screened before joining the experiments. A medical doctor conducted physical examination, electrocardiogram, blood pressure and routine blood tests. A successful psychiatric interview was necessary to join the experiment. Other exclusion criteria were 1) under 18 years of age, 2) having no previous experience with psychedelic drugs, 3) history of diagnosed psychiatric illnesses, 4) excessive use of alcohol (more than 40 units per week). The day before the experiment a urine and pregnancy test (when applicable) were performed, together with a breathalyzer test. Participants attended 2 sessions, in the first one, they received placebo, while DMT was administered in the second session. Given the lack of human data with DMT, progressively increasing doses were provided to different participants (4 different doses were used: 7mg, 14mg, 18mg and 20mg, to 3, 4, 1 and 5 successive participants respectively). EEG signals were recorded before and up to 20 minutes after drug delivery. Participants rested in a semi-supine position with their eyes closed during the duration of the whole experiment. The eyes closed instruction was confirmed by visual inspection of the participants during dosing. At each minute, participants provided an intensity rating, while blood samples were taken at given time-points (the same for placebo and DMT conditions) via a cannula inserted in the participants' arm. One day after the DMT session, participants reported their subjective experience completing an interview composed of several questionnaires (seefor details). In this study we focused on the Visual Analogue Scale values. EEG preprocessing. EEG signals were recorded using a 32-channels Brainproduct EEG system sampling at 1000Hz. A high-pass filter at 0.1Hz and an anti-aliasing lowpass filter at 450Hz were applied before applying a band-pass filter at 1-45Hz. Epochs with artifacts were manually removed upon visual inspection. Independent-component analysis (ICA) was performed and components corresponding to eye-movement and cardiac-related artifacts were removed from the EEG signal. The data were rereferenced to the average of all electrodes. All the preprocessing was carried out using the Fieldtrip toolbox, while the following analysis were run using custom scripts in MATLAB . Waves quantification. We epoched the preprocessed EEG signals in 1 second windows, sliding with a step of 500ms (see figure). For each time window, we then arranged a 2D time-electrode map composed of 5 electrodes (i.e. Oz, POz, Pz, Cz, FCz). From each map we computed the 2D Fast Fourier Transform (2DFFT -fig.), from which we extracted the maximum value in the upper and lower quadrants, representing respectively the power of forward (FW) and backward (BW) waves. We also performed the same procedure 100 times after having randomized the electrodes' order: the surrogate 2D-FFT spectrum has the same temporal frequency content overall, but the spatial information is disrupted, and the information about the wave directionality is lost. In such a manner we obtained the null or surrogate measures, namely FWss and BWss, whose values are the average over the 100 repetitions (see figure). Eventually, we computed the actual amount of waves in decibel (dB), considering the log-ratio between the actual and the surrogate values: It is worth noting that this value represents the amount of significant waves against the null distribution, that is against the hypothesis of having no FW or BW waves.
All the analyses regarding the EEG signals were performed in Matlab. Bayesian analyses were run in JASP. We ran separate Bayesian ANOVA for FW and BW conditions, and we considered as factors the time of injection (prepost, see figure) and drug condition (DMT vs Placebo). Subjects were considered to account for random factors. Regarding the minute-by-minute analysis (figure, right panels) we performed a t-test at each time-bin against zero, and we corrected all the p-values according to the False Discovery Rate 46 .
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Muthukumaraswamy, S. D., Carhart-Harris, R. L., Moran, R. J. et al. · Journal of Neuroscience (2013)
Schartner, M., Carhart-Harris, R. L., Barrett, A. B. et al. · Scientific Reports (2017)
Carhart-Harris, R. L., Friston, K. J. · Pharmacological Reviews (2019)
Carhart-Harris, R. L. · World Psychiatry (2018)
Strassman, R. J. · Journal of Nervous and Mental Disease (1995)
Barker, S., McIlhenny, E. H., Strassman, R. J. · Drug Testing and Analysis (2012)
De Araujo, D. B., Ribeiro, S., Cecchi, G. A. et al. · Human Brain Mapping (2011)
Palhano-Fontes, F., Andrade, K. C., Tófoli, L.F. et al. · PLOS ONE (2015)
Pink-Hashkes, S., Van Rooij, I., Kwisthout, J. · CogSci (2017)
Carhart-Harris, R. L., Muthukumaraswamy, S., Roseman, L. et al. · PNAS (2016)
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Tarailis, P., Griskova-Bulanova, I. · Biorxiv (2026)
Mäki-Marttunen, V. · Communications Biology (2026)
Blackburne, G., Mcalpine, R. G., Fabus, M. et al. · Cell Reports (2025)
Henry, J., Giribaldi, B., Nutt, D. J. et al. · European Neuropsychopharmacology (2025)
Wießner, I., Falchi-Carvalho, M., Laborde, S. et al. · European Neuropsychopharmacology (2025)
Zeifman, R. J., Spriggs, M. J., Kettner, H. et al. · Scientific Reports (2025)
McGovern, H., Grimmer, H. J., Doss, M. K. et al. · Communications Psychology (2024)
Shinozuka, K., Tewarie, P. K. B., Luppi, A. et al. · Biorxiv (2024)
Pasquini, L., Simon, A. J., Gallen, C. L. et al. · Biorxiv (2024)
Luan, L. X., Eckernäs, E., Ashton, M. et al. · Journal of Psychopharmacology (2023)
Lawrence, D. W., Timmermann, C. · Journal of Psychoactive Drugs (2023)
Michael, P., Luke, D., Robinson, O. · Frontiers in Psychology (2023)
Timmermann, C., Roseman, L., Haridas, S. et al. · PNAS (2023)
Carhart-Harris, R. L., Chandaria, S., Erritzoe, D. E. et al. · Neuropharmacology (2023)
Aqil, M., Roseman, L. · Neuropharmacology (2022)
Kwan, A. C., Olson, D. E., Preller, K. H. et al. · Nature Medicine (2022)
Gattuso, J. J., Perkins, D., Ruffell, S. G. D. et al. · International Journal of Neuropsychopharmacology (2022)
Luppi, A. I., Hansen, J. Y., Adapa, R. et al. · Biorxiv (2022)
Hipólito, I., Mago, J., Rosas, F. E. et al. · Psyarxiv (2022)
Jiménez, J. H., Bouso, J. C. · Journal of Psychopharmacology (2022)
Lawrence, D. W., Carhart-Harris, R. L., Griffiths, R. R. et al. · Research Square (2022)
Dursun, S. M., Kelly, J. R., Gillan, C. M. et al. · Frontiers in Psychiatry (2021)
Zamani, A., Carhart-Harris, R. L., Christoff, K. · Neuropsychopharmacology (2021)
Deane, G. · Neuroscience of Consciousness (2021)
Domenico, C., Haggerty, D., Mou, X. et al. · Cell Reports (2021)
Burt, J. B., Preller, K. H., Demirtaş, M. et al. · eLife (2021)
Kočárová, C., Horacek, J., Carhart-Harris, R. L. · Frontiers in Psychiatry (2021)
Michael, P., Luke, D., Robinson, O. · Frontiers in Psychology (2021)
Brouwer, A., Carhart-Harris, R. L. · Journal of Psychopharmacology (2020)
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