Intriguing Synergies Between Hallucinatory Conditions The interplay between increasing excitation via the coupling constants (e. g., a, c) and via the Input term in Equation 1 suggests that condition pairings that drive both should interact synergisti-cally. Five lines of evidence support this: (a) Subjects given asubhallucinatory dose of mescaline immediately perceivemescaline-quality geometric hallucinations (more intense and or-nate than those normally seen in flicker) when exposed to flick-ering light (Smythies, 1960). Similarly, Knoll, Kuger, Höffer, and Lawder (1963) reported similar hallucinatory interactions betweenelectrical cortical stimulation and several hallucinogenic drugs. (b) As discussed above, when flicker is synchronized to the subject'salpha EEG rhythm, pattern formation is 3 to 5 times faster than forunsynchronized trials (Shevelev et al., 2000). (c) Oster (1970)reported that LSD flashbacks (see Figures 1A-1D) are easilyevoked by ocular pressure, and Klu ¨ver (1966) reported that in the early prehallucinatory stage of intoxication, ocular pressure speedsdrug hallucinations. Similarly, Siegel's (1992) patient triggered LSD flashbacks (resembling Figure 1F) with flickering neonlights, but only after heavy stimulant (nicotine and caffeine) use. Inkeeping with this, about 83% of heavy amphetamine abusers reporthallucinations as a side effect (Paulseth & Klawans, 1985). Anumber of studies are consistent with a net excitatory effect ofhallucinogenic drugs on the visual system (Winters, 1975). Forexample, LSD increases visual evoked responses at both the lateralgeniculate nucleus (LGN) and cortex (Purpura, 1956a, 1956b). Interestingly, diphenylhydantoin, a drug used to treat epilepsy bydampening neural excitability (usually by deactivating some so-dium channels in neural membranes), is also effective in suppress-ing LSD flashbacks (Thurlow & Girvin, 1971), and subjects with LSD flashbacks show an epileptic-like increase in the coherence of EEG in the absence of stimulation (Abraham & Duffy, 2001). (d)Migraineurs, based on many lines of evidence, appear to be chron-ically hyperexcitable (Aurora & Wilkinson, 2007) and, most rel-evantly here, between attacks have reduced thresholds for TMS-induced phosphenes (Aurora et al., 1998). The same reduction inphosphene-induction thresholds has been documented in Ecstasyusers who hallucinate (Oliveri & Calvo, 2003). (e) Flicker triggershallucinatory auras in some migraineurs and epileptics. Like ordi-nary flicker-induced and ocular-pressure-induced hallucinations,photo-induced epileptic auras are easier to obtain for two eyes thanone (Hess, Harding, & Drasdo, 1974). Moreover, in animals dosedwith GABA-antagonists (which block inhibition), a migraine-likecortical wave is triggered by flicker (van Harreveld & Stamm,1955). Many of these interactions make sense as a synergy be-tween excitability (internal parameters set by neural wiring anddrug dosage) and the Input term (an external variable tapped by flicker, ocular pressure, and TMS) of Equation 1; both mecha-nisms increase excitation in a spatially homogeneous way. Con-sider a pedestal of internal activation to which external stimulationis added: If the combined effects of steady internal activation andtransient external stimulation exceed a critical level, then patternformation occurs. In the case of drug flashbacks, previous hallu-cinatory experiences may influence the long-term value of Equa-tion 1's a-dparameters via Hebbian learning. Experimental Evidence of Spontaneous Pattern Formation in Visual Cortex Many hallucinations are explained by models based on Ermen-trout and Cowan (1979). Yet the Ermentrout-Cowan model'sgreater significance may be that it suggests that autonomous neuralactivity could be perceptually meaningful. This has become animportant issue in sensory neuroscience (Arieli, Sterkin, Grinvald,& Aertsen, 1996; Kenet, Bibitchkov, Tsodyks, Grinvald, & Arieli,2003; Ringach, 2003, 2009). It has long been known that evenunstimulated visual cortex forms neural patterns; once thought tobe mere noise, this activity is spatiotemporally structured and mayinteract in perceptually significant ways with spatiotemporal ac-tivity induced by images. For example, Kenet et al. (2003) usedvoltage-sensitive dyes to make high-resolution video recordings ofneural activity in the visual cortex of anesthetized and unstimu-lated cats; this autonomous cortical activity is highly structuredand matches cortical activity induced in the same animals byviewing oriented grating patterns (see Figure 10; Kenet et al., 2003; Ringach, 2003). These autonomously formed patterns arereminiscent of the Ermentrout-Cowan patterns; Goldberg, Rokni,and Sompolinsky (2004) treated both the Kenet et al. and Ermentrout-Cowan patterns as subsets of attractors in a dynamicphase space of neural states visited by the underlying nonlineardynamic system, an interpretation reinforced by recent work onneural attractor dynamics (Ghosh, Rho, Mc Intosh, Kötter, & Jirsa,2008; Luczak, Bartho, & Harris, 2009; Ringach, 2009). Thisdescription is supported by Kenet et al. 's (2003) results: Thespontaneous neural activity continually and unpredictablyswitched between states describing different grating orientations,reminiscent of the unpredictability of the Ermentrout-Cowanmodel and the instability of many induced hallucinations. Ofcourse, Kenet's patterns (if present in unanesthetized humans) aresubliminal, since we do not perceive illusory oriented gratingswherever we look; Ringach (2009) suggested that sensory depri-vation hallucinations (including clinical conditions like CBS) maystem from these patterns becoming visible. However, even sub-threshold neural patterns could alter perception by interacting withstimulated activity. Opponent Interactions Between Hallucinations and Stimulus-Generated Activity Several lines of evidence suggest that cortical pattern formation interacts with stimulus-generated cortical activity to influence per-ception. Wilkinson (2004) proposed that the ictal blindness thatfollows visual epilepsy may be the result of high autonomousactivity in visual cortex that never settles into an organized pattern,interfering with stimulus-driven visual activity without giving riseto percepts of its own. More prosaically, Fiser, Chiu, and Weliky(2004) showed that as cortex ages, the cortical modulation ofsensory input by the underlying activity changes as well. Billockand Tsou (2007, 2010) attacked the problem from the other direc-tion, using small physical stimuli to bias the otherwise randomhallucinations evoked by flickering light. Previous studies of self-organized pattern formation in nonlinear dynamic systems foundthat pattern-forming systems could be biased by introducing afeature that was aligned in the desired orientation. For example, in Figure 8, a fluid-dynamic system forms oriented cylinders of rising759 HALLUCINATIONS AND CORTICAL PATTERN FORMATION