Dexamphetamine increased speech and visual unimodal illusions in healthy participants without affecting temporal binding window.

OBJECTIVE: Stimuli received beyond a very short timeframe, known as temporal binding windows (TBWs), are perceived as separate events. In previous audio-visual multisensory integration (McGurk effect) studies, widening of TBWs has been observed in people with schizophrenia. The present study aimed to determine if dexamphetamine could increase TBWs in unimodal auditory and unimodal visual illusions that may have some validity as experimental models for auditory and visual hallucinations in psychotic disorders. METHODS: A double-blind, placebo-controlled, counter-balanced crossover design with permuted block randomisation for drug order was followed. Dexamphetamine (0.45 mg/kg, PO, q.d.) was administered to healthy participants. Phantom word illusion (speech illusion) and visual-induced flash illusion/VIFI (visual illusion) tests were measured to determine if TBWs were altered as a function of delay between stimuli presentations. Word emotional content for phantom word illusions was also analysed. RESULTS: Dexamphetamine significantly increased the total number of phantom words/speech illusions (p < 0.01) for pooled 220-1100 ms ISIs in kernel density estimation and the number of positive valence words heard (beta = 2.20, 95% CI [1.86, 2.55], t = 12.46, p < 0.001) with a large effect size (std. beta = 1.05, 95% CI [0.89, 1.22]) relative to placebo without affecting the TBWs. For the VIFI test, kernel density estimation for pooled 0-801 ms ISIs showed a significant difference (p < 0.01) in the data distributions of number of target flash (es) perceived by participants after receiving dexamphetamine as compared with placebo. CONCLUSIONS: Overall, healthy participants who were administered dexamphetamine (0.45 mg/kg, PO, q.d.) experienced increases in auditory and visual illusions in both phantom word illusion and VIFI tests without affecting their TBWs.

Embodied Precision: Intranasal Oxytocin Modulates Multisensory Integration.

Multisensory integration processes are fundamental to our sense of self as embodied beings. Bodily illusions, such as the rubber hand illusion (RHI) and the size-weight illusion (SWI), allow us to investigate how the brain resolves conflicting multisensory evidence during perceptual inference in relation to different facets of body representation. In the RHI, synchronous tactile stimulation of a participant's hidden hand and a visible rubber hand creates illusory body ownership; in the SWI, the perceived size of the body can modulate the estimated weight of external objects. According to Bayesian models, such illusions arise as an attempt to explain the causes of multisensory perception and may reflect the attenuation of somatosensory precision, which is required to resolve perceptual hypotheses about conflicting multisensory input. Recent hypotheses propose that the precision of sensorimotor representations is determined by modulators of synaptic gain, like dopamine, acetylcholine, and oxytocin. However, these neuromodulatory hypotheses have not been tested in the context of embodied multisensory integration. The present, double-blind, placebo-controlled, crossover study ( n = 41 healthy volunteers) aimed to investigate the effect of intranasal oxytocin (IN-OT) on multisensory integration processes, tested by means of the RHI and the SWI. Results showed that IN-OT enhanced the subjective feeling of ownership in the RHI, only when synchronous tactile stimulation was involved. Furthermore, IN-OT increased an embodied version of the SWI (quantified as estimation error during a weight estimation task). These findings suggest that oxytocin might modulate processes of visuotactile multisensory integration by increasing the precision of top-down signals against bottom-up sensory input.

Topiramate-induced palinopsia: a case series and review of the literature.

BACKGROUND: To report palinopsia as a possible side effect of topiramate. METHODS: Case series and review of the literature. RESULTS: Nine patients in our series, and 4 previously reported patients, who developed palinopsia while on topiramate, are reviewed. All patients were women, and comorbidities included migraine, idiopathic intracranial hypertension, and bulimia nervosa. Palinopsia resolved in 8 patients after stopping or decreasing the dose of topiramate. The lowest dose of topiramate causing palinopsia was 25 mg twice a day. More than half of our patients reported exacerbation of visual disturbance in early morning or late evening. CONCLUSIONS: Topiramate-induced palinopsia may be underdiagnosed because physicians do not inquire about such visual symptoms.

Pharmacological Enhancement of Dopamine Neurotransmission Does Not Affect Illusory Pattern Perception.

Psychotic symptoms and delusional beliefs have been linked to dopamine transmission in both healthy and clinical samples and are assumed to result at least in part from perceiving illusory patterns in noise. However, the existing literature on the role of dopamine in detecting patterns in noise is inconclusive. To address this issue, we assessed the effect of manipulating dopaminergic neurotransmission on illusory pattern perception in healthy individuals (n = 48, n = 19 female) in a double-blind placebo-controlled within-subjects design (see preregistration at https://osf.io/a4k9j/). We predicted individuals on versus off ʟ-DOPA to be more likely to perceive illusory patterns, specifically objects in images containing only noise. Using a signal detection model, however, we found no credible evidence that ʟ-DOPA compared with placebo increased false alarm rates. Further, ʟ-DOPA did not reliably modulate measures of accuracy, discrimination sensitivity, and response bias. In all cases, Bayesian statistics revealed strong evidence in favor of the null hypothesis. The task design followed previous work on illusory pattern perception and comprised a limited number of items per condition. The results therefore need to be interpreted with caution, as power was limited. Future studies should address illusory pattern perception using more items and take into account potential dose-dependent effects and differential effects in healthy versus clinical samples.

Anomalous bodily-self experiences among recreational ketamine users.

INTRODUCTION: Out-of-body experiences present a unique paradigm to investigate cognitive and neural mechanisms of bodily-self processes and their disorders. Previous work on out-of-body experiences associated with sleep paralysis supported a model in which illusory movement experiences reflect disrupted bodily-self integration generating anomalous vestibular and motor sensations. Further disintegration and progression of the experience may then give rise to out-of-body feelings, which in turn may instigate out-of-body autoscopy. METHODS: The current study assesses the disintegration model through analyses of out-of-body experiences reports from an online survey of individuals reporting recreational ketamine use (n=128) and cross-validation in a sample of nonketamine polydrug users (n=64). Path analyses using intensity and frequency measures of anomalous experiences assess the fit of seven competing models. RESULTS: The disintegration model (illusory movement → out-of-body feelings → out-of-body autoscopy) emerged as the best fitting model overall and results support full mediation of the relation between illusory movement experiences and out-of-body autoscopy by out-of-body feelings. Moreover, lifetime measures of ketamine use predicted the frequency of illusory movement experiences. CONCLUSIONS: The results corroborate this structural model of out-of-body phenomena and encourage a framework for future studies into aetiological mechanisms of out-of-body experiences to include neurochemical systems.

Impaired visual hand recognition in preoperative patients during brachial plexus anesthesia: importance of peripheral neural input for mental representation of the hand.

BACKGROUND: Perceptual illusions described in healthy subjects undergoing regional anesthesia (RA) are probably related to short-term plastic brain changes. We addressed whether performance on an implicit mental rotation task reflects these RA-induced changes in body schema brain representations. Studying these changes in healthy volunteers may shed light on normal function and the central mechanisms of pain. METHODS: Performance pattern was studied in upper limb-anesthetized subjects on a left/right hand judgment task, which is known to involve motor imagery processes relating to hand posture. Three conditions were used: control (i.e., absence of deafferentation), RA (i.e., deafferentation), and vision (i.e., deafferentated limb exposed to view). To limit potential bias such as order effect, the control state was recorded in a randomized manner. RESULTS: All subjects described perceptual illusions of their anesthetized limb. They were slower and less accurate on the task during RA compared with control. Response patterns were similar in all conditions, suggesting sensitivity of performance to arm/hand biomechanical constraints. Vision was associated with an increase in the proportion of correct responses and a reduction of the response times in hand judgment and was accompanied by disappearance of the lateralization of the underlying mental representations, which was identified during RA. CONCLUSIONS: These results suggest the following: (1) the right/left judgment task involves mental simulation of hand movements, (2) underlying mental representations and their neural substrates are subject to acute alterations after RA, and (3) the proprioceptive deficit induced by RA is influenced by the subject's ability to see the anesthetized limb.

The Territory of my Body: Testosterone Prevents Limb Cooling in the Rubber Hand Illusion.

The Rubber Hand Illusion (RHI) is an experimental paradigm for assessing changes in body ownership. Recent findings in the field suggest that social emotions can influence such changes and that empathic motivation in particular appears to positively predict the malleability of body representations. Since the steroid hormone, testosterone, is well known to interrupt certain forms of empathic processing, in the current study we investigated whether 0.5 mg of testosterone affected ownership indices of the RHI. Forty-nine females participated in a double-blind, placebo-controlled experiment in which the RHI was induced. Compared to placebo, testosterone had no effects on the alteration of subjective ownership over the rubber limb or on subjective sense of proprioceptive drift. However, unlike the placebo group, testosterone-treated participants did not display an objective decline in the temperature of their own (hidden) hand following induction of the illusion. These findings suggest that testosterone strengthens implicit but not explicit bodily self-representations. We propose that effective maintenance of implicit body boundaries can be regarded, conceptually, as a primary defensive state facilitating integrity of the self.

MK-801 reduces sensitivity to Müller-Lyer's illusion in capuchin monkeys.

The Müller-Lyer's illusion (MLI) is a visual illusion in which the presence of contextual cues (i.e., the orientation of arrowheads) changes the perception of the length of straight lines. An altered sensitivity to the MLI has been proposed as a marker for the progression of perceptual deficits in schizophrenia. Since dizocilpine (MK-801), a noncompetitive antagonist of the NMDA glutamate receptor, induces schizophrenic-like sensory impairments, it may have potential value for investigating the neurochemical basis of the perceptual changes in schizophrenia. Here we tested the effects of MK-801 on the perception of the MLI in a nonhuman primate. Five capuchin monkeys Sapajus spp. were trained on a MLI task using a touch screen monitor. After training, the Point of Subjective Equality (PSE; i.e., the minimum difference in length between two lines which the subject can distinguish) was determined for each subject. Then, during 12 consecutive days, we evaluated changes in PSE in response to vehicle, MK-801 (5.6µg/kg, i.m.) and a no-treatment protocol (post- test). Each of these was given as a single daily treatment, on four consecutive days. Results showed that MK-801 increased the monkeys' performance in the MLI task, suggesting that NMDA receptor modulation reduces sensitivity to this illusion, similar to prodromal stage in schizophrenia patients. The MLI protocol may thus be used in nonhuman primates to screen potential antipsychotic drugs for early stages of this disease.

JWH-122 Consumption Adverse Effects: A Case of Hallucinogen Persisting Perception Disorder Five-Year Follow-Up.

Synthetic cannabinoid receptor agonists are a heterogeneous group of psychotropic drugs functionally related to Δ9-tetrahydrocannabinol. These substances, marketed as cannabis substitutes, have been associated with numerous cases of severe intoxication and death across the world. In our article, we describe a case of hallucinogen persisting perception disorder developing in a natural cannabis user after consumption of JWH-122, a naphthoylindole largely used since 2010. Clinical symptomatology persisted for about four years and was alleviated through treatment with clonazepam. Considering that natural cannabis consumption can induce the development of a hallucinogen persisting perception disorder, it is not excluded that, in our patient, symptoms lasted a long time due to cannabis consumption. This article describes the clinical evolution from onset to resolution of all symptoms.

Sympathomimetic-induced kaleidoscopic visual illusion associated with a reversible splenium lesion.

BACKGROUND: Sympathomimetic-induced metabolic derangements within the central nervous system can result in conspicuous changes in neurological functioning and corresponding radiographic abnormalities that can be reversible. OBJECTIVE: To describe a patient with a "kaleidoscopic" visual illusion who was found by magnetic resonance imaging to have a transient lesion in the splenium of the corpus callosum. DESIGN: Case report. SETTING: The University of Texas Southwestern Medical Center, Dallas. PATIENT: A 17-year-old adolescent girl who developed an episode of kaleidoscopic vision while using sympathomimetic-containing diet pills that was associated with a reversible lesion of the splenium of the corpus callosum. Her brother has a history of migraine and experienced a similar episode while using illicit stimulant agents. INTERVENTION: Withdrawal of the medication resulted in the cessation of the episodes and normalization of the magnetic resonance image. MAIN OUTCOME MEASURES: Clinical and radiographic improvement. RESULTS: Sympathomimetic-induced metabolic derangements can be associated with reversible lesions within the brain. CONCLUSIONS: We hypothesize that the visual fragmentation was a manifestation of a migraine triggered by sympathomimetic-containing diet pills, and that the transient lesion in the corpus callosum was a manifestation of a reversible metabolic derangement. Both the visual fragmentation and the lesion in the corpus callosum resolved once the patient stopped receiving diet pills.

Intracisternal administration of mitogen-activated protein kinase inhibitors reduced IL-1beta-induced mirror-image mechanical allodynia in the orofacial area of rats.

The present study investigated the role of central mitogen-activated protein kinases (MAPKs) in interleukin-1beta (IL-1beta)-induced mirror-image mechanical allodynia in the orofacial area. Experiments were carried out on Sprague-Dawley rats. Under pentobarbital sodium anesthesia, a polyethylene tube was implanted in the subcutaneous area of one vibrissa pad, which enabled us to inject IL-1beta. For an intracisternal injection, each anesthetized rat was mounted on a stereotaxic frame and a polyethylene tube was implanted. Animals were given a recovery time of at least 72 h from surgery. After a subcutaneous administration of 0.01, 0.1, 1, or 10 pg of IL-1beta, we examined the face withdrawal behavioral responses produced by 10 successive trials of air puffs ipsilateral or contralateral to the IL-1beta injection site. Normal animals did not respond to pressure less than 40 psi. The thresholds of air puffs ipsilateral and contralateral to the IL-1beta injection site were significantly lower in the IL-1beta-treated group, compared with the vehicle-treated group. The decrease in the threshold of air puffs appeared 10 min after an IL-1beta injection and persisted for over 3h. Intracisternal pretreatment with PD98059, a p44/42 MAPK inhibitor, or SB203580, a p38 MAPK inhibitor, significantly reduced the decrease in the threshold of air puffs ipsilateral to the IL-1beta injection site produced by 10 pg of IL-1beta. IL-1beta-induced mirror-image mechanical allodynia was also reduced significantly by intracisternal pretreatment with both PD98059 and SB203580. These results indicate that central MAPK pathways mediate IL-1beta-induced mirror-image mechanical allodynia in the orofacial area.

Chronic administration of ketamine mimics the perturbed sense of body ownership associated with schizophrenia.

RATIONALE: Subanaesthetic ketamine infusion in healthy volunteers induces experiences redolent of early psychosis, including changes in the experience of one's own body. It is not clear, however, whether repeated self-administration of ketamine has a sustained effect on body representation that is comparable to that found during acute administration. OBJECTIVES: We sought to establish whether chronic ketamine use resulted in disturbances to sense of body ownership. METHODS: Following on from our work on the effects of acute ketamine infusion, we used the rubber hand illusion (RHI) to experimentally manipulate the sense of body ownership in chronic ketamine users, compared to healthy controls. RESULTS: Chronic ketamine users experienced the RHI more strongly and reported more body-image aberrations, even though they had not recently taken the drug. CONCLUSIONS: These findings suggest that the chronic ketamine model for psychosis models more long-lasting changes in sense of ownership, perhaps more akin to schizophrenia.

Benzodiazepines and semantic memory: effects of lorazepam on the Moses illusion.

RATIONALE: When asked "How many animals of each kind did Moses take on the ark?", people fail to notice the distortion introduced by the impostor "Moses" and respond "two". It has been argued that the effect must be due to the existence of a partial-match process. In most situations, the form of a question is not likely to closely match the memory representation it queries. Thus, for the partial match hypothesis people ignore some semantic distortions. In the same vein, it has been shown that the benzodiazepine lorazepam drug induces some impairments of semantic memory as participants under lorazepam provide more incorrect recalls than placebo do with general information questions. OBJECTIVES: The aim of this study was to investigate the effects of the benzodiazepine lorazepam on the Moses illusion paradigm. METHOD: The effects of lorazepam (0.038 mg/kg) and of a placebo were investigated in 28 healthy volunteers. Twenty-two illusory questions were presented along with 72 normal general information questions. RESULTS: Lorazepam impaired the ability to detect the Moses illusion. Moreover, lorazepam participants appeared less biased to consider a question distorted than placebo participants. CONCLUSIONS: The temporary and reversible semantic memory impairments experienced by participants when falling into the Moses illusion are more frequent under lorazepam. The amnesic drug lorazepam may impair semantic processing as well as the strategic control of memory.

Effects of synthetic delta9-tetrahydrocannabinol on binocular depth inversion of natural and artificial objects in man.

Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic delta9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The timecourse of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.

Modification of visual orientation illusions by drugs which influence dopamine and GABA neurones: differential effects on simultaneous and successive illusions.

The effects of haloperidol, nomifensine and lorazepam on the visual tilt illusion were studied in normal volunteers. Haloperidol and nomifensine produced no significant changes in the illusion, although in previous work they had been found to reduce and enhance, respectively, a closely related illusion, the tilt aftereffect. By contrast, lorazepam produced a dose-related increment in the size of the tilt illusion, but had no effect on the tilt aftereffect. The results are discussed in relation to proposed mechanisms which may underlie the two kinds of illusion. The differential effects of individual drugs on the two illusions may reflect their differing actions on two processes: lateral inhibition and adaptation in visual channels.

Effects of a low dose of alcohol on recollective experience of illusory memory.

RATIONALE: Memory illusions are currently a focus of memory research. Studies using the Deese/Roediger and McDermott paradigm have shown a differential pattern of illusory memories is associated with amnesia and ageing. The effects of pharmacological agents in this paradigm are not yet known. OBJECTIVE: Using this paradigm, the present study investigated the effects of a low dose of alcohol upon recollective experience of illusory memories. METHODS: A double-blind cross-over design was used to compare the effects of alcohol (0.26-0.28 g.kg-1) with a matched placebo drink. RESULTS: High levels of false recognition were obtained across both treatments, replicating previous results. Although the small dose of alcohol employed did not produce gross changes in measures of false memory, it did modify the pattern of recollective experience in terms of remember and know responses. Specifically, it increased the level of remember responses for falsely recognised items (critical lures). CONCLUSION: These results are discussed in terms of ethanol's effects on false recognition of information which was not presented during the study episode. The effects of low dose alcohol on illusory memory are similar to the pattern found in ageing rather than that found in organic amnesia.

The effects of scopolamine and cyclizine on visual-vestibular interaction in humans.

The aim of the present study was to investigate the effects of scopolamine (1.5 mg, transdermal patch) and cyclizine (50 mg tablet), at the doses usually used for the relief of motion sickness, on postural sway, optokinetic nystagmus (OKN) and circularvection (CV) in humans, using a within-subjects, double-blind, placebo-controlled design. Scopolamine and cyclizine were found to have no significant suppressive effect on these aspects of visual-vestibular interaction. Postural sway and CV were not significantly affected by either drug treatment; OKN SPV was significantly increased (p < 0.05), although OKN amplitude and frequency were unaffected. These results suggest that scopolamine and cyclizine, at doses used for the relief of motion sickness, may have minimal suppressive effects on these aspects of visual-vestibular interaction.