Koro: a socially-transmitted delusional belief.

INTRODUCTION: Koro is a delusion whereby a man believes his penis is shrinking into his abdomen and this may result in his death. This socially-transmitted non-neuropsychological delusional belief occurs (in epidemic form) in South-East and South Asia. We investigated whether the two-factor theory of delusion could be applied to epidemic Koro. METHODS: We scrutinised the literature on epidemic Koro to isolate features relevant to the two questions that must be answered to provide a two-factor account: What could initially prompt the Koro delusional hypothesis? Why is this hypothesis adopted as a belief? RESULTS: We concluded that the Koro hypothesis is usually prompted by the surprising observation of actual penis shrinkage-but only if the man has access to background beliefs about Koro. Whether the hypothesis is then adopted as a belief will depend on individual factors such as prior belief in the Koro concept or limited formal education and sociocultural factors such as deference to culture, to media, or to rumours spread by word of mouth. Social transmission can influence how the first factor works and how the second factor works. CONCLUSION: The two-factor theory of delusion can be applied to a socially-transmitted delusion that occurs in epidemic form.

Inattentional blindness: Attentional set for efficient task success.

Inattentional blindness is the failure to notice an unexpected object in plain sight when attention is otherwise engaged. We investigated what determines observers' attentional set in a dynamic-counting inattentional blindness paradigm, when task instructions and visual distinctiveness of task-relevant objects were either congruent or in opposition. In seven experiments, observers counted bounces by task-relevant objects, with the instruction either to count-by-shape (squares, diamonds, crosses) or count-by-colour (blue, purple). To manipulate visual distinctiveness, we varied the extent to which task-relevant and task-irrelevant objects looked different on two dimensions: shape and colour. When colour better distinguished task-relevant from task-irrelevant objects, observers-even if instructed count-by-shape-reported an unexpected object that matched the colour of task-relevant objects. Crucially, when instructed count-by-colour, but shape better distinguished task-relevant from task-irrelevant objects, observers reported an unexpected object that matched the shape of task-relevant objects. We conclude that observers set their attention to promote efficient task performance.

Cotard delusion, emotional experience and depersonalisation.

INTRODUCTION: Cotard delusion-the delusional belief "I am dead"-is named after the French psychiatrist who first described it: Jules Cotard. Ramachandran and Blakeslee proposed that the idea "I am dead" comes to mind when a neuropathological condition has resulted in complete abolition of emotional responsivity to the world. The idea would arise as a putative explanation: if "I am dead" were true, there would be no emotional responsivity to the world. METHODS: We scrutinised the literature on people who expressed the delusional belief "I am dead", looking for data on whether such patients are reported as entirely lacking in emotional responsivity. RESULTS: In numerous cases, patients with Cotard delusion are described as experiencing emotions including anxiety, fear, guilt, distress, euphoria and worry. CONCLUSIONS: We conclude that complete absence of emotional responsivity cannot be what prompts the delusional idea that one is dead. We propose that, in at least some cases, the idea "I am dead" comes to mind in response to symptoms of depersonalisation or derealisation, often present in cases of Cotard delusion, and give examples of Cotard patients with abnormalities in various neural areas that could be responsible for the presence of such symptoms.

What is Capgras delusion?

INTRODUCTION: Capgras delusion is sometimes defined as believing that close relatives have been replaced by strangers. But such replacement beliefs also occur in response to encountering an acquaintance, or the voice of a familiar person, or a pet, or some personal possession. All five scenarios involve believing something familiar has been replaced by something unfamiliar. METHODS: We evaluate the proposal that these five kinds of delusional belief should count as subtypes of the same delusion. RESULTS: Personally familiar stimuli activate the sympathetic nervous system (SNS) much more strongly than unfamiliar stimuli. In Capgras delusion, this difference is absent, prompting the delusional idea that a familiar person is actually a stranger. We suggest this absence of an effect of familiarity on SNS response will occur in all five scenarios and will prompt the idea that the familiar has been replaced by the unfamiliar. CONCLUSIONS: We propose that: (a) all five scenarios be referred to as subtypes of Capgras delusion; (b) in all five, ideas about replacement are prompted by weakness of SNS responses to familiar stimuli; (c) this is insufficient to generate delusion. For a delusional idea to become a belief, a second factor (impaired hypothesis evaluation) must also be present.

A phase II, Multicentre, Randomised, Double-Blind, Placebo-controlled Study to Evaluate Safety, Tolerability, and Efficacy of Amiselimod in Patients with Moderate to Severe Active Crohn's Disease.

BACKGROUND AND AIMS: Amiselimod is an oral selective S1P1 receptor modulator with potentially fewer adverse effects than fingolimod. We evaluated the safety, tolerability, and clinical efficacy of amiselimod in participants with moderate to severe active Crohn's disease. METHODS: This was a phase IIa, multicentre, randomised, double-blind, parallel group, placebo-controlled study comparing amiselimod 0.4 mg with placebo over a 14-Week treatment period. The primary endpoint of the study was the proportion of participants with clinical response (Crohn's Disease activity Index [CDAI] 100) from baseline at Week 12. RESULTS: A total of 180 patients were screened and 78 were randomised [40 to amiselimod 0.4 mg and 38 to placebo]. There was no significant difference in the proportion of patients achieving CDAI 100 at Week 12 on amiselimod 0.4 mg and on placebo [48.7% vs. 54.1%, respectively] (odds ratio [OR] [95% confidence interval]: 0.79 [0.31, 1.98]). The results from the secondary endpoint analyses supported the results of the primary endpoint analysis. Treatment with amiselimod 0.4 mg was generally well tolerated, with 71.8% of participants completing the 14-week treatment period. Seven participants had serious adverse events and four discontinued treatment in the amiselimod group. CONCLUSIONS: Amiselimod 0.4 mg for 12 weeks was not superior to placebo for the induction of clinical response [CDAI 100] in Crohn's disease. Treatment with amiselimod 0.4 mg was generally well tolerated and no new safety concerns related to amiselimod were reported in this study.

Effects of Symmetry and Apparent Distance in a Parasagittal-Mirror Variant of the Rubber Hand Illusion Paradigm.

When I see my face in a mirror, its apparent position (behind the glass) is not one that my own face could be in. I accept the face I see as my own because I have an implicit understanding of how mirrors work. The situation is different if I look at the reflection of my right hand in a parasagittal mirror (parallel to body midline) when my left hand is hidden behind the mirror. It is as if I were looking through a window at my own left hand. The experience of body ownership has been investigated using rubber hand illusion (RHI) paradigms, and several studies have demonstrated ownership of a rubber hand viewed in a frontal mirror. Our "proof of concept" study was the first to combine use of a parasagittal mirror and synchronous stroking of both a prosthetic hand (viewed in the mirror) and the participant's hand, with a manipulation of distance between the hands. The strength of the RHI elicited by our parasagittal-mirror paradigm depended not on physical distance between the hands (30, 45, or 60 cm) but on apparent distance between the prosthetic hand (viewed in the mirror) and the participant's hand. This apparent distance was reduced to zero when the prosthetic hand and participant's hand were arranged symmetrically (e.g., 30 cm in front of and behind the mirror). Thus, the parasagittal-mirror paradigm may provide a distinctive way to assess whether competition for ownership depends on spatial separation between the prosthetic hand and the participant's hand.

Failure of hypothesis evaluation as a factor in delusional belief.

INTRODUCTION: In accounts of the two-factor theory of delusional belief, the second factor in this theory has been referred to only in the most general terms, as a failure in the processes of hypothesis evaluation, with no attempt to characterise those processes in any detail. Coltheart and Davies ([2021]. How unexpected observations lead to new beliefs: A Peircean pathway. Consciousness and Cognition, 87, 103037. https://doi.org/10.1016/j.concog.2020.103037) attempted such a characterisation, proposing a detailed eight-step model of how unexpected observations lead to new beliefs based on the concept of abductive inference as introduced by Charles Sanders Peirce. METHODS: In this paper, we apply that model to the explanation of various forms of delusional belief. RESULTS: We provide evidence that in cases of delusion there is a specific failure of the seventh step in our model: the step at which predictions from (delusional) hypotheses are considered in the light of relevant evidence. CONCLUSIONS: In the two-factor theory of delusional belief, the second factor consists of a failure to reject hypotheses in the face of disconfirmatory evidence.

How unexpected observations lead to new beliefs: A Peircean pathway.

People acquire new beliefs in various ways. One of the most important of these is that new beliefs are acquired as a response to experiencing events that one did not expect. This involves a form of inference distinct from both deductive and inductive inference: abductive inference. The concept of abduction is due to the American pragmatist philosopher C. S. Peirce. Davies and Coltheart (in press) elucidated what Peirce meant by abduction, and identified two problems in his otherwise promising account requiring solution if that account were to become fully workable. Here we propose solutions to these problems and offer an explicit cognitive model of how people derive new beliefs from observations of unexpected events, based on Peirce's work and Sokolov's ideas about prediction error triggering new beliefs. We consider that this model casts light not only upon normal processes of belief formation but also upon the formation of delusional beliefs.

Inattentional blindness on the full-attention trial: Are we throwing out the baby with the bathwater?

When attention is otherwise engaged, observers may experience inattentional blindness, failing to notice objects or events that are presented in plain sight. In an inattentional blindness experiment, an unexpectedstimulus ispresented alongside primary-task stimuli, and its detection is probed. We evaluate a criterion that is commonly used to exclude observers from the data analysis. On the final experimental trial, observers do not perform the primary task, but instead look for anything new. Observers who fail to report the unexpected stimulus on thisfull-attention trialare excluded. On the basis of 4 hypothetical experiments and a review of 128 actual experiments from the literature, we demonstrate some potentially problematic consequences of implementing the full-attention-trial exclusion criterion. Excluded observers may cluster in experimental conditions and the exclusion criterion may lead researchers to understate the pervasiveness of inattentional blindness. It may even render usblindto inattentional blindness on the full-attention trial.

Two-year results from a phase 2 extension study of oral amiselimod in relapsing multiple sclerosis.

BACKGROUND: Amiselimod, an oral selective sphingosine-1-phosphate 1 receptor modulator, suppressed disease activity dose-dependently without clinically relevant bradyarrhythmia in a 24-week phase 2, placebo-controlled study in relapsing-remitting multiple sclerosis. OBJECTIVE: To assess safety and efficacy of amiselimod over 96 weeks. METHODS: After completing the core study, patients on amiselimod continued at the same dose, whereas those on placebo were randomised 1:1:1 to amiselimod 0.1, 0.2 or 0.4 mg for another 72 weeks. Most patients receiving 0.1 mg were re-randomised to 0.2 or 0.4 mg upon availability of the core study results. RESULTS: Of 415 patients randomised in the core study, 367 (88.4%) entered and 322 (77.6%) completed the extension. One or more adverse events were reported in 303 (82.6%) of 367 patients: 'headache', 'lymphocyte count decreased', 'nasopharyngitis' and 'MS relapse' were most common (14.7%-16.9%). No serious opportunistic infection, macular oedema or malignancy was reported and no bradyarrhythmia of clinical concern was observed by Holter or 12-lead electrocardiogram. The dose-dependent effect of amiselimod on clinical and magnetic resonance imaging-related outcomes from the core study was sustained in those continuing on amiselimod and similarly observed after switching to active drug. CONCLUSION: For up to 2 years of treatment, amiselimod was well tolerated and dose-dependently effective in controlling disease activity.