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Background: The pathophysiology of psychosis is complex, but a better understanding of stimulus binding windows (BWs) could help to improve our knowledge base. Previous studies have shown that dopamine release is associated with psychosis and widened BWs. We can probe BW mechanisms using drugs of specific interest to psychosis. Therefore, we were interested in understanding how manipulation of the dopamine or catecholamine systems affect psychosis and BWs. We aimed to investigate the effect of dexamphetamine, as a dopamine-releasing stimulant, on the BWs in a unimodal illusion: the tactile funneling illusion (TFI). Methods: We conducted a randomized, double-blind, counterbalanced placebo-controlled crossover study to investigate funnelling and errors of localization. We administered dexamphetamine (0.45 mg/kg) to 46 participants. We manipulated 5 spatial (5-1 cm) and 3 temporal (0, 500 and 750 ms) conditions in the TFI. Results: We found that dexamphetamine increased funnelling illusion (p = 0.009) and increased the error of localization in a delay-dependent manner (p = 0.03). We also found that dexamphetamine significantly increased the error of localization at 500 ms temporal separation and 4 cm spatial separation ([p.sub.interaction] = 0.009; [p.sub.500ms14cm v. baseline] = 0.01). Limitations: Although amphetamine-induced models of psychosis are a useful approach to understanding the physiology of psychosis related to dopamine hyperactivity, dexamphetamine is equally effective at releasing noradrenaline and dopamine, and, therefore, we were unable to tease apart the effects of the 2 systems on BWs in our study. Conclusion: We found that dexamphetamine increases illusory perception on the unimodal TFI in healthy participants, which suggests that dopamine or other catecholamines have a role in increasing tactile spatial and temporal BWs., Introduction People integrate multiple stimuli over space and time to form unified percepts of objects and events, (1) and alterations in integration have been proposed as being important for a [...]

Abnormally widened spatial and temporal binding windows (SBW/TBWs; length of space/time whereby stimuli are considered part of the same percept) are observed in schizophrenia. TBW alterations have been associated with altered sense of agency (hereafter referred to as agency), and an associative relationship between embodiment (body ownership) and agency has been proposed. SBWs/TBWs are investigated separately, but no evidence exists of these being separate in mechanism, system or function. The underlying neural substrate of schizophrenia remains unclear. The literature claims either pro-psychotic or anti-psychotic effects of Δ9-Tetrahydrocannabinol (THC) in patients and healthy individuals, but major support for cannabis in the aetiology of schizophrenia is associative, not causal. To clarify if THC is pro- or anti-psychotic, this single-blind, placebo-controlled within-subjects cross-over study tested several hypotheses. 1) Competing hypotheses that a synthetic THC analogue, Nabilone (NAB, 1–2 mg), would alter measures of agency and embodiment in healthy volunteers (n = 32) similarly, or opposite, to that of in patients with schizophrenia. 2) That there would be significant associations between any NAB-induced alterations in individual agency and embodiment measures in the Projected Hand Illusion (PHI). 3) That there is a unitary spatio-temporal binding window (STBW). A large proportion of individuals did not experience the PHI. Multimodal and bi-directional effects of NAB on the PHI were observed. Evidence of a unitary spatio-temporal binding window (STBW) was observed. NAB widened the STBW in some but narrowed it in others as a function of space and delay. No associations were found between agency and embodiment. [ABSTRACT FROM AUTHOR]

Background: An emerging endophenotype of schizophrenia is the reduction of both power and phase locking of the 40 Hz auditory steady state response (ASSR), and there have been a number of reports linking increased y activity with positive psychotic symptoms. Schizophrenia and, more specifically, positive psychotic symptoms have been closely linked to increased dopamine (DA) neurophysiology. Therefore, we gave dexamphetamine to healthy participants to determine the effect that increased DA transmission would have on the ASSR. Methods: We administered 0.45 mg/kg of dexamphetamine orally in a double-blind placebo-controlled crossover study. Stimuli were 20 Hz and 40 Hz click trains presented in an auditory oddball-type stimulus format (probability of stimulus presentation: 0.2 for targets, 0.8 for nontargets). Results: We included 44 healthy volunteers (18 women) in the study. Dexamphetamine significantly increased the 40 Hz power for both target and nontarget ASSR stimuli. Dexamphetamine did not significantly affect the 40 Hz phaselocking factor (PLF) or the 20 Hz power and PLF. Whereas there were significant effects of selective attention on power and PLF for 20 and 40 Hz ASSR, there were no significant interactions between dexamphetamine and selective attention. Limitations: Dexamphetamine releases both noradrenaline and DA with equal potency. Further research with selective dopaminergic and noradrenergic agents will better characterize the effects of monoamines on y activity. Conclusion: The results demonstrate a frequency- specific effect of dexamphetamine on the ASSR. This finding is consistent with previous research that has found an association between increased y and positive symptoms of psychosis. However, this result also raises the possibility that previous 40 Hz ASSR findings in people with schizophrenia may be confounded by effects of antipsychotic medication. Possible neural mechanisms by which dexamphetamine specifically increases 40 Hz power are also discussed. Australian and New Zealand Clinical Trials Registry number: ACTRN12608000610336., Introduction An emerging endophenotype of schizophrenia is the reduction of both power and phase locking of the 40 Hz auditory steady state response (ASSR). (1-7) It is not just people [...]

The reduced P3 is one of the most robust deficits involved in schizophrenia. Previous research with catecholaminergic agonists or releasers such as amphetamines have used doses too small to adequately demonstrate an effect on P3. In this study, we gave 0.45 mg/kg dexamphetamine to healthy volunteers (final n = 18) using both auditory and visual three-stimulus P3 procedures. Dexamphetamine significantly reduced P3 amplitudes to auditory target, rare non-target and standard stimulus amplitudes. The reduction in auditory P3 induced by dexamphetamine was proportional across stimulus types to placebo P3 values. There were no effects of dexamphetamine on visual P3. We demonstrate a reduced auditory P3 similar to that seen in schizophrenia and other psychotic illnesses. This possibly reflects a common pathology which is hypothesized within the P3 literature to be related to attention and working memory. Differences between auditory and visual P3 modulation may be related to regional variations in catecholamine or specifically dopamine receptor densities. One specific auditory P3 generator is the superior temporal cortex, an area with dopamine D2 receptor enriched bands. This is contrasted with visual specific generators, such as the inferior temporal cortex and superior parietal cortex, which do not have these enriched bands. [ABSTRACT FROM PUBLISHER]

Objectives Methods Results Conclusions Stimuli that are separated by a short window of space or time, known as spatial and temporal binding windows (SBW/TBWs), may be perceived as separate. Widened TBWs are evidenced in schizophrenia, although it is unclear if the SBW is similarly affected. The current study aimed to assess if dexamphetamine (DEX) may increase SBWs in a multimodal visuo‐tactile illusion, potentially validating usefulness as an experimental model for multimodal visuo‐tactile hallucinations in schizophrenia, and to examine a possible association between altered binding windows (BWs) and working memory (WM) suggested by previous research.A placebo‐controlled, double‐blinded, and counter‐balanced crossover design was employed. Permuted block randomisation was used for drug order. Healthy participants received DEX (0.45 mg/kg, PO, b.i.d.) or placebo (glucose powder) in capsules. The Rubber Hand Illusion (RHI) and Wechsler Adult Intelligence Scale Spatial Span was employed to determine whether DEX would alter SBWs and WM, respectively. Schizotypy was assessed with a variety of psychological scales.Most participants did not experience the RHI even under normal circumstances. Bi‐directional and multimodal effects of DEX on individual SBWs and schizotypy were observed, but not on WM.Bidirectional multimodal effects of DEX on the RHI and SBWs were observed in individuals, although not associated with alterations in WM. [ABSTRACT FROM AUTHOR]