DMT alters cortical travelling waves

N,N, Dimethyltryptamine (DMT) is a mixed serotonin receptor agonist that occurs endogenously in several organisms (Christian et al., 1977; Nichols, 2016) including humans (Smythies et al., 1979), albeit in trace concentrations. 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 (Buckholtz and Boggan, 1977). 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 min and subsiding thereafter, with negligible effects felt after about 30 min (Strassman, 2001; Strassman, 1995a; Timmermann et al., 2019).

Previous electrophysiological studies investigating changes in spontaneous (resting state) brain function elicited by ayahuasca have reported consistent broadband decreases in oscillatory power (Riba et al., 2002; Timmermann et al., 2019), while others have noted that the most marked decreases occur in α-band oscillations (8–12 Hz) (Schenberg et al., 2015). Alpha decreases correlated inversely with the intensity of ayahuasca-induced visual hallucinations (Valle et al., 2016) and are arguably the most reliable neurophysiological signature of the psychedelic state identified to-date (Muthukumaraswamy et al., 2013) – with increased signal diversity or entropy being another particularly reliable biomarker (Schartner et al., 2017). 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 was observed as well as increase in signal diversity (Timmermann et al., 2019). Increase 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 effects – consolidating 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 (Lozano-Soldevilla and VanRullen, 2019; Muller et al., 2014; Sato et al., 2012). 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 (Alamia and VanRullen, 2019; Halgren et al., 2019; Pang et al., 2020).

Taken together these results compel us to ask how travelling waves may be affected by DMT, particularly given their association with predictive coding (Alamia and VanRullen, 2019; Friston, 2019) and a recent predictive coding inspired hypothesis on the action of psychedelics (‘REBUS’) – which posits decreased top-down processing and increased bottom-up signal passing under these compounds (Carhart-Harris and Friston, 2019). 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’ (de Araujo et al., 2012) – 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 favour of the latter (Carhart-Harris and Friston, 2019). Moreover, we ask: does this effect correlate with the vivid ‘visionary’ component of the DMT experience? Providing evidence in favour 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.