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.

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.

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.

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.

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.

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.

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.

[Visual experiences during cataract surgery under topical anesthesia]. / Visuelle Erlebnisse unter Kataraktchirurgie in topischer Anästhesie.

BACKGROUND: Cataract patients observe structures, colors and movements during surgery. Is there any pattern to their visual experiences? METHODS: From 2005 to 2011 a total of 20,000 phacoemulsification procedures were performed using topical anesthesia. From these patients we received 45 pictures which had been painted to reflect intraoperative their visual impressions so that approximately 1 out of 500 of the patients painted a picture. A further 98 patients were questioned postoperatively about their intraoperative visual impressions and were shown the 45 pictures. They described their own visual experiences and any similarities with the 45 pictures were documented. RESULTS: All patients were awake and cooperative during surgery. Afterwards they described their visual experiences whereby 36 patients saw mainly blue, 32 red/pink and 27 saw yellow colors. Out of the 45 pictures 30 (67%) were identified as being similar to their own visual images and 10 patients could not describe any postoperative visual phenomena. CONCLUSION: Patients notice optical phenomena during cataract surgery under topical anesthesia with eye drops. Visual images are often similar among patients. The surgeon can use this knowledge to explain these experiences while talking to the patient intraoperatively. This may reassure patients during surgery.

Alcohol consumption enhances vection.

We assessed changes in forward vection following alcohol consumption, and found that alcohol consumption enhanced vection. This result indicates that alcohol can affect psychophysical processes responsible for self-motion perception.

Palinopsia induced by topiramate and zonisamide in a patient with migraine.

Palinopsia is an illusory visual phenomenon consisting in the persistence or recurrence of visual images after the exciting stimulus object has been removed. It has been reported in association with parietal and occipital lobe lesions, migraine auras, and related to the use of several drugs and illicit drugs. Here, we report the case of a 23-year-old woman with a 4-year history of episodic migraine with aura who developed palinopsia during sequential prophylactic therapies with topiramate and zonisamide. Although the exact physiopathology of this phenomenon remains unknown, topiramate- and zonisamide-induced palinopsia support an increase on serotonergic activity as a possible mechanism for this visual disorder.

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.

The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease.

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward.

Dexamphetamine effects on separate constructs in the rubber hand illusion test.

RATIONALE: Corporeal awareness is an integral component of self-consciousness and is distorted in several neurological and psychiatric disorders. Research regarding the neural underpinnings of corporeal awareness has made much progress recently using the rubber hand illusion (RHI) procedure. However, more studies are needed to investigate the possibility of several dissociable constructs related to the RHI specifically, and corporeal awareness generally. OBJECTIVES: Considering dopamine's involvement in many perceptual-motor learning processes, as well as its apparent relationship with disorders such as schizophrenia that are linked to body ownership disturbances, we gave 0.45 mg/kg dexamphetamine (a dopamine transporter reverser) to 20 healthy participants to examine the effects of increased dopamine transmission on the RHI. METHODS: The effect of dexamphetamine on separate quantitative constructs underlying RHI were examined including embodiment of rubber hand, loss of ownership of real hand, perception of movement, affect, deafference, and proprioceptive drift. The experiment was a double-blind, placebo-controlled, cross-over design. RESULTS: Dexamphetamine increased participants' ratings of embodiment (particularly "ownership") of the rubber hand and was associated with the experience of loss of ownership of the person's real hand. There were significant increases from asynchronous to synchronous stroking for the measures of movement and proprioceptive drift after placebo but not dexamphetamine. There were no changes in the measures of other constructs. CONCLUSIONS: These results show a novel pharmacological manipulation of separate constructs of the RHI. This finding may aid in our understanding of disorders that have overlapping disturbances in both dopamine activity and body representations, particularly schizophrenia.