Effects on Visual Perception

Binocular rivalry is a phenomenon that occurs when different images are simultaneously presented to each eye. When continually viewing this stimulus, observers

experience repeated switches between visual aware- ness of the two images. Frecska et al. (2004) examined the effects of the hallucinogenic brew ayahuasca on binocular rivalry in 10 subjects. As noted earlier, ayahuasca is a decoction made from two Amazonian plants, containing DMT as the active psychedelic component, and b-carboline alkaloids that inhibit the liver MAO that normally breaks down orally ingested DMT. Hence, ayahuasca might essentially be consid- ered to be an orally active form of DMT. In this study, a variant of stimulus presentation called dichoptic stim- ulus alternation (DSA) was employed. In DSA, stimuli are applied to the eyes in rapid alterations instead of keeping the stimulus presented to each eye constant. The stimuli consisted of white binocular fixation guides centered within which is a disk filled either with horizontal or vertical gratings. Standard binocular rivalry was presented for 6 minutes to obtain the endogenous perceptual alternation rate. Dichoptic re- versal stimuli were presented at 3.75, 7.5, 15, and 30 reversals per second in four 1.5-minute epochs. At a low DSA rate of 3.75 or 7.5 Hz, normal subjects reported horizontal and vertical switching at a very high rate. At 15 and 30 Hz DSA, however, a blended percept (cross- hatch) was consistently reported. By contrast, after subjects had ingested ayahuasca, they were able to maintain much longer horizontal or vertical dominance periods, even when the stimuli were alternating at rates almost two orders of magnitude faster than their endogenous rivalry rate. To explain their results, the authors favor a view that the persistence of binocular rivalry at high DSA rates “requires a neural context that involves the primary visual cortex and visual pathways below.”

Carter et al. (2004) studied whether psilocybin could impair motion processing in humans. They found that a 215-mg/kg dose of psilocybin selectively impaired global motion, but not local motion processing in nine healthy human subjects. They argue that because local motion discrimination is thought to be a relatively low-level process resolvable at the level of primary visual cortex V1, the lack of effect of psilocybin on local motion thresholds indicates that visual disturbances associ- ated with the drug do not likely reflect changes at the level of the retina or in transfer of information from the retina through the lateral geniculate nucleus to primary visual cortex.

Carter et al. (2005b) studied perceptual rivalry with low-dose (115mg/kg) and high-dose (250mg/kg) psilocy- bin in 12 healthy human volunteers. Stationary green vertical and horizontal gratings were presented to the subject’s left eye and right eye, respectively. Vertical and horizontal gratings were presented alternately, in rapid succession at 120 Hz. Subjects reported a domi- nance of vertical gratings by pressing one computer key, and by pressing another when they experienced a dominance of horizontal gratings. They could also

respond if they experienced a stable mixed percept (grid or patchwork). Psilocybin dose-dependently increased binocular rivalry phase duration in a manner reflecting subjective changes in state of consciousness, as assessed with the 5D-ASC rating scale developed by Dittrich (1998).

Carter et al. (2007) explored the proposed relation- ship between binocular rivalry switch rate and sub- jective changes in psychologic state associated with 5-HT2A receptor activation. Ten healthy human sub- jects were tested after administration of psilocybin (215mg/kg) and after pretreatment with the selective 5-HT2A antagonist ketanserin (50 mg). Psilocybin significantly reduced the rate of binocular rivalry switching. Pretreatment with 50 mg ketanserin blocked most of psilocybin’s positive psychosis-like hallucino- genic effects but had no effect on the suppression of binocular rivalry switching induced by psilocybin, indi- cating that the psilocybin-induced rate reduction likely was not mediated by 5-HT2Areceptor activation.

Carter et al. (2005a) investigated the effects of psilocybin (215 mg/kg, p.o.) on attentional function in eight healthy volunteers using a multiple-object track- ing task. The task required subjects to track a subset (up to eight) of 20 visually indistinguishable randomly moving green dots. This task is believed to test an individual’s capacity to maintain multiple foci of atten- tion simultaneously. They also tested spatial working memory using an electronic version of Corsi’s block tapping task, in which subjects were required to re- member and reproduce a sequence of up to nine spatial locations. Because the effects of psilocybin are thought to be mediated primarily by activation of the 5-HT2A receptor, the selective 5-HT2A antagonist ketanserin (50 mg, p.o.) was used to determine whether it would attenuate any psilocybin-induced changes in atten- tional tracking or spatial working memory. The 5D- ASC rating scale (Dittrich, 1998) was also used to assess the subjective effects of the drug.

Carter et al. (2005a) found that psilocybin signifi- cantly increased four of the five factors in the 5D-ASC, but only the factor of reduced vigilance remained significantly elevated after ketanserin pretreatment. Performance on the tracking task varied inversely with the number of targets subjects had to track, and it dropped off markedly when the number of targets exceeded three. The number of dots successfully tracked was significantly reduced from placebo in both the psilocybin and psilocybin plus ketanserin pretreatment conditions; ketanserin alone had no effect. In the spatial working memory task, psilocybin had no significant effect on the number of boxes remembered correctly in sequence“span length,”indicating that psilocybin had no effect on spatial working memory performance. Thus, psilocybin impaired multiple-object tracking through a non–5-HT2Areceptor–dependent mechanism but had no effect on spatial working memory. In view of

the fact that psilocybin has agonist actions at the 5-HT2A, 5-HT2C, and 5-HT1A receptors, the authors suggest that the deficit in attentional tracking might be due to the 5-HT1Areceptor agonist action of psilocybin. In that event, activation of somatodendritic autoreceptors in the raphe would lead to a reduction of 5-HT release into forebrain regions, possibly disrupting multiple-tracking ability mediated by those regions and consistent with work from other laboratories suggesting involvement of 5-HT and the 5-HT1Areceptor in attention (see references in Carter et al., 2005a).

To further characterize the role of 5-HT1A/2Areceptors in visual processing, Kometer et al. (2011) assessed the effect of psilocybin (125 and 250 mg/kg) versus placebo on spatiotemporal dynamics of modal object completion in 17 healthy volunteers. Modal object recognition refers to the illusory perception of object boundaries and their enclosing surface when there is no direct sensory information to depict those boundaries or surfaces. The authors employed visual evoked potential recordings in conjunction with topographic mapping and source analysis. EEG recordings were made while participants viewed Kanizsa and non-Kanizsa figures. Behavioral responses were recorded and high-density electrical mapping with source analysis was used, allowing for the measurement of the spatiotemporal brain dynamics of visual modal object completion and its association with the appearance of visual hallucina- tions. Imaging studies have provided evidence that the intermediate lateral occipital complex (LOC) as well as the early visual area V2 probably play a major role in modal completion. Electrophysiological studies have demonstrated that modal object completion of simple figures such as Kanizsa figures is predominantly indexed by modulation of the N170 component (see references in Kometer et al., 2011).

Kometer et al. (2011) found that psilocybin increased reaction time, which was generally faster for Kanizsa than for non-Kanizsa figures. After psilocybin treat- ment, the P1 amplitude (90–144 milliseconds) was increased and was locally restricted to occipital elec- trode sites. Psilocybin dose-dependently decreased the N170 amplitude (148–223 milliseconds). Source esti- mation revealed activity within LOC and V2 in both hemispheres, with current source density stronger within the right-lateralized LOC and V2 in the Kanizsa compared with the non-Kanizsa condition. Psilocybin dose-dependently decreased the differential activation of the two stimulus conditions and reduced the current source density within the LOC, V2, and fusiform gyrus in both stimulus conditions. Psilocybin-induced current source-density reduction over the right-lateralized LOC, V2, and posterior parietal areas correlated signif- icantly with the increased intensity of visual hallucina- tions. The three main findings of this study were as follows. First, there was a strong dose-dependent effect of psilocybin to decrease the N170 component, but there

was a slight increase of the earlier visual P1 component over occipital sites. Second, the N170 component re- duction was stronger for the Kanizsa figure condition than for the non-Kanizsa condition. Third, during this time range, the decrease in activation over the right- lateralized extrastriate and posterior parietal cortex was correlated with the reported intensity of visual hallucinations. The preferential reduction of the N170 amplitude in the Kanizsa compared with the non- Kanizsa condition indicates a key role for 5-HT1A/2A receptor(s) in object completion. Reduced extrastriate visual cortex activation during the time range of the N170 also identifies it as a potential key component of 5-HT2Aagonist–induced visual hallucinations.

Kometer et al. (2013) used a similar experimental approach to assess the effects of psilocybin on both a

oscillations that regulate cortical excitability and early visual P1 and N170 potentials in 17 healthy humans. They also tested whether these effects were related to the formation of visual hallucinations. Parieto-occipital

a oscillations are crucial for modulation of visual network excitability and strongly influence visual per- ception (see references in Kometer et al., 2013). The authors hypothesized that activating 5-HT2Areceptors with psilocybin might modulateaoscillations, leading to an altered excitability that would promote visual hallucination formation. They used a double-blind, placebo-controlled randomized design, in which sub- jects received pretreatments of placebo or ketanserin (50 mg, p.o.) and treatments of placebo or psilocybin (215mg/kg). Stimuli were Kanizsa figures that induce the perception of an illusory triangle, or non-Kanizsa figures in which the figure alignment no longer induces that perception. EEG data were recorded and the P1 and N170 amplitudes were quantified, with a time frame from 80–120 milliseconds for the P1 and 150– 190 milliseconds for the N170 amplitude.

Kometer et al. (2013) report that psilocybin robustly induced visual perceptual alterations that included complex visual hallucinations of scenes and pictures, visual elementary hallucinations of regular patterns, colors, light, and light flashes, but no such effects occurred after ketanserin pretreatment. Psilocybin selectively increased P1 amplitudes over the medial but not the lateral parieto-occipital regions of interest, and the psilocybin-induced increase over the medial region was blocked by ketanserin. The N170 amplitudes were decreased by psilocybin, and this effect was blocked by ketanserin. Correlation analysis with the original five main factors of the 5D-ASC revealed that the N170 decrease was selectively associated with visual perceptual alterations. Psilocybin also strongly decreased prestimulusapower (i.e., 98–12 Hz;2600 to

2200 milliseconds), most evident in the right parieto- occipital region, and this decrease also was prevented by ketanserin pretreatment. The psilocybin-induced decrease ina power was significantly correlated with

the psilocybin-induced increase in the medial P1 visual potential. The high level of prestimulus a power was strongly attenuated by psilocybin, and this effect was reversed by ketanserin pretreatment, suggesting that 5-HT2Areceptor activation increases excitability of the visual network in the absence of externally presented stimuli by decreasing ongoing a oscillations. Further- more, the strongly decreased prestimulus a power by psilocybin precluded observation of any subsequent stimulus-induced decrease in a power. The authors conclude that 5-HT2A receptor activation induces a “dysbalance” between the excitability observed in the absence of an external stimulus and the excitability induced by the presentation of a stimulus, which occurs primarily by an attenuation of ongoing a oscillations. The fact that both the N170 potentials and perceptual alterations were blocked by ketanserin pretreatment led the authors to suggest that the decrease in N170 potentials is a crucial mechanism underlying 5-HT2A receptor–mediated alterations of visual perception.

de Araujo et al. (2012) investigated the neural basis of imagery induced by the psychedelic Amazonian brew ayahuasca. They studied 10 regular ayahuasca users who participated in two fMRI sessions. The first scan was performed on the subjects before taking ayahuasca, after which they immediately drank ayahuasca. Psychologic changes were assessed at various times, and became significant at 40 and 80 minutes after ingestion. The second fMRI session began 40 minutes after drug intake when effects were at their maximum. Subjects performed three different visual tasks. First, they passively viewed natural images of people, animals, or trees. Then they were asked to close their eyes and mentally generate the same image they had just seen. Finally, they viewed a scrambled version of the image. Statistically significant brain areas of blood oxygen level–dependent (BOLD) signal increase were observed after ayahuasca intake, compared with the predrug condition. The increase in the BOLD signal was most pronounced in the bilateral occipital cortex, extending into the inferior and medial temporal lobe, and to parts of the frontal lobe. The signal amplitude after ayahuasca intake increased markedly in occipital areas during imagery, but not when viewing natural images. The activity of several cortical areas known to be involved in episodic memory and contextual association processing was also potentiated by ayahuasca during the imagery task. A connectivity analysis revealed that ayahuasca strongly altered fronto-occipital relation- ships, leading to marked changes in the timing of events across several brain regions. de Araujo et al. (2012) speculate that the robust visions induced by ayahuasca may even be initiated in the primary visual cortex.