Examining the presence and nature of delusions in Alzheimer's disease and frontotemporal dementia syndromes.

OBJECTIVES: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a transdiagnostic, cross-sectional approach. METHODS: Four-hundred and eighty-seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural-variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy. All patients underwent neuropsychological assessment and brain magnetic resonance imaging, and the Neuropsychiatric Inventory was conducted with an informant, by an experienced clinician. RESULTS: In our cohort, 48/487 patients (10.8%) had delusions. A diagnosis of behavioural-variant frontotemporal dementia (18.4%) and Alzheimer's disease (11.8%) were associated with increased risk of delusions. A positive gene mutation was observed in 11/27 people with delusions. Individuals with frequent delusions performed worse on the Addenbrooke's Cognitive Examination (p = 0.035), particularly on the orientation/attention (p = 0.022) and memory (p = 0.013) subtests. Voxel-based morphometry analyses found that increased delusional psychopathology was associated with reduced integrity of the right middle frontal gyrus, right planum temporale and left anterior temporal pole. CONCLUSION: Our results demonstrate that delusions are relatively common in dementia and uncover a unique cognitive and neural profile associated with the manifestation of delusions. Clinically, delusions may lead to delayed or misdiagnosis. Our results shed light on how to identify individuals at risk of neuropsychiatric features of dementia, a crucial first step to enable targeted symptom management.

Appearance-based trust processing in schizophrenia.

OBJECTIVES: Schizophrenia is characterized by impaired social interactions and altered trust. In the general population, trust is often based on facial appearance, with limited validity but enormous social consequences. The aim was to examine trust processing in schizophrenia and specifically to examine how people with schizophrenia use facial appearance as well as actual partner fairness to guide trusting decisions. DESIGN: An experimental economic game study. METHODS: Here, we tested how patients with schizophrenia and control participants (each N = 24) use facial trustworthiness appearance and partner fairness behaviour to guide decisions in a multi-round Trust Game. In the Trust Game, participants lent money to 'partners' whose facial appearance was either untrustworthy or trustworthy, and who either played fairly or unfairly. Clinical symptoms were measured as well as explicit trustworthiness impressions. RESULTS: Overall, the patients with schizophrenia showed unimpaired explicit facial trustworthiness impressions and unimpaired facial appearance biases in the Trust Game. Crucially, patients and controls significantly differed so that the patients with schizophrenia did not learn to discriminate in the Trust Game based on actual partner fairness, unlike control participants. CONCLUSION: A failure to discriminate trust has important implications for everyday functioning in schizophrenia, as forming accurate trustworthiness beliefs is an essential social skill. Critically, without relying on more valid trust cues, people with schizophrenia may be especially susceptible to the misleading effect of appearance when making trusting decisions. PRACTITIONER POINTS: Findings People with schizophrenia made very similar facial trustworthiness impressions to healthy controls and also used facial appearance to guide trust decisions similarly to controls. However, the patient group were less able to explicitly distinguish between fair and unfair partners based on their behaviour compared with the control group. Moreover, people with schizophrenia failed to use actual partner fairness to guide their financial decisions in the Trust Game, unlike controls, and this impairment was specific to a social task. People with schizophrenia may be particularly reliant on facial appearance when trusting others, as they may struggle to incorporate more valid trustworthiness information in their decision-making, such as actual partner fairness.

Perceiving and attributing intentionality in schizophrenia.

Introduction: People with schizophrenia perform poorly on theory-of-mind (ToM) tasks. They also generate less mental-state language to describe test stimuli depicting intentionality. Some of these individuals also show excessive mentalising when objective cues of intentionality are absent. We tested perceiving and attributing intentionality to resolve this paradox. Methods: 23 schizophrenia patients and 20 healthy controls completed the chasing detection task to assess perceptual sensitivity to cues of intentionality. Other tasks assessed spontaneous attributions of intentionality (irrespective of accuracy) and accurate ToM inferences. Results: Perceptual sensitivity to cues of intentionality did not differ between groups. Patients were less likely to spontaneously attribute intentionality (irrespective of accuracy) or perform ToM tasks accurately. Chasing-detection response bias, but not perceptual sensitivity, correlated with attributions of intentionality. Referential (and to less extent) persecutory ideation associated with excessive mentalising when cues of intentionality were absent. Conclusions: Intentionality can be directly perceived, independent of attributions or inferences, in people with schizophrenia. We conclude that the flow of information from intact perceptual detection to evoke spontaneous attributions of intentionality is disrupted in schizophrenia, with flow-on detrimental effects on accurate ToM reasoning. Referential/persecutory ideation motivates inappropriate mentalising when objective cues of intentionality are absent.

Impairments of spontaneous and deliberative mentalizing co-occur, yet dissociate, in schizophrenia.

OBJECTIVES: Evidence of impairment in explicit mentalizing in people with schizophrenia has inspired interventions to improve awareness of others' mental states in these individuals. Less is known of implicit mentalizing in schizophrenia, with current findings mixed. We sought to resolve previous inconsistencies using Heider & Simmel's (H&S) classic animation to elicit spontaneous mentalizing and examined relations between spontaneous and deliberative mentalizing. METHODS: Forty-five schizophrenia outpatients and 27 general-community controls completed two explicit theory-of-mind (TOM) tasks and then described the H&S animation (to elicit spontaneous social attributions about emotionally driven, as well as goal-driven, behaviours), before and after an instruction to think of the shapes as people. Accuracy of basic and social facts and frequencies of personification and different mental-state terms were recorded. RESULTS: Explicit TOM performance was impaired in patients. Patients also generated fewer social (but not basic) facts than controls to describe the H&S animation, and used less mental-state language, before, and even more so, after the 'people' instruction, despite that both groups had used more personification terms after the 'people' instruction. Measures of explicit and spontaneous mentalizing contributed independently to discriminating between groups. CONCLUSIONS: Patients respond less to the bottom-up signals of agency that ought normally to elicit spontaneous social attributions, even when cued to think of the stimuli as people, and the stimuli depict emotionally driven, as well as goal-driven, behaviour. That impairments of spontaneous and deliberative mentalizing dissociate in schizophrenia suggests that training deliberative mentalizing may not be enough; interventions to improve spontaneous mentalizing are also needed. PRACTITIONER POINTS: Findings People with schizophrenia were less likely than controls to spontaneously attribute causal mental states when viewing dynamic signals of emotionally driven and goal-driven behaviours. These impairments were even more pronounced when participants were instructed to think of the stimuli as people, suggesting that perceiving others in social roles does not prompt people with schizophrenia to anthropomorphize about others as agents motivated by their own inner worlds. Impairments of spontaneous mentalizing were found to co-occur independently with explicit mentalizing deficits in schizophrenia, consistent with the claim that humans can access two distinct systems for understanding others' minds. Findings suggest that interventions to improve conscious deliberative mentalizing in schizophrenia may not be enough; we also need to target implicit mentalizing processes. Limitations The patient sample was chronic and only mildly symptomatic. As such, findings cannot be generalized to other stages and phases of the illness. All patients were also medicated, allowing for the possibility that automatic responses to socially salient stimuli may have been pharmacologically attenuated. Future research may examine whether unmedicated young people at ultra-high risk of psychosis show a similar profile of mentalizing impairment. Future work may also examine whether impairments of deliberative and spontaneous mentalizing associate differentially with social functioning and different cognitive domains in schizophrenia.

Masked and unmasked priming in schizophrenia.

Dehaene et al. (2003) showed an absence of conscious, but not masked, conflict effects when patients with schizophrenia performed a number-categorisation priming task. We aimed to replicate these influential results using a different word-categorisation priming task. Counter to Dehaene et al.'s findings, 21 patients and 20 healthy controls showed similar congruence effects for both masked and visible primes. Within patients, a reduced congruence effect for visible primes associated with longer duration of illness and more severe behavioural disorganisation. Patients, unlike controls, were no slower to respond to targets that followed visible compared to masked primes. Conscious conflict effects on priming tasks are not universally reduced in schizophrenia but may associate with chronicity and behavioural disorganisation. That patients were no slower when the preceding primes were clearly visible accords with evidence elsewhere that information processing in schizophrenia is driven more by immediate conscious experience and constrained less by prior events.

Should I trust you? Autistic traits predict reduced appearance-based trust decisions.

Facial impressions of trustworthiness guide social decisions in the general population, as shown by financial lending in economic Trust Games. As an exception, autistic boys fail to use facial impressions to guide trust decisions, despite forming typical facial trustworthiness impressions (Autism, 19, 2015a, 1002). Here, we tested whether this dissociation between forming and using facial impressions of trustworthiness extends to neurotypical men with high levels of autistic traits. Forty-six Caucasian men completed a multi-turn Trust Game, a facial trustworthiness impressions task, the Autism-Spectrum Quotient, and two Theory of Mind tasks. As hypothesized, participants' levels of autistic traits had no observed effect on the impressions formed, but negatively predicted the use of those impressions in trust decisions. Thus, the dissociation between forming and using facial impressions of trustworthiness extends to the broader autism phenotype. More broadly, our results identify autistic traits as an important source of individual variation in the use of facial impressions to guide behaviour. Interestingly, failure to use these impressions could potentially represent rational behaviour, given their limited validity.

Belief, delusion, hypnosis, and the right dorsolateral prefrontal cortex: A transcranial magnetic stimulation study.

According to the Two-Factor theory of delusional belief (see e.g. Coltheart at al., 2011), there exists a cognitive system dedicated to the generation, evaluation, and acceptance or rejection of beliefs. Studies of the neuropsychology of delusion provide evidence that this system is neurally realized in right dorsolateral prefrontal cortex (rDLPFC). Furthermore, we have shown that convincing analogues of many specific delusional beliefs can be created in nonclinical subjects by hypnotic suggestion and we think of hypnosis as having the effect of temporarily interfering with the operation of the belief system, which allows acceptance of the delusional suggestions. If the belief system does depend on rDLPFC, then disrupting the activity of that region of the brain by the application of repetitive transcranial magnetic stimulation (rTMS) will increase hypnotizability. Dienes and Hutton (2013) have reported such an experiment except that it was left DLPFC to which rTMS was applied. An effect on a subjective measure of hypnotizability was observed, but whether there was an effect on an objective measure could not be determined. We report two experiments. The first was an exact replication of the Dienes and Hutton experiment; here we found no effect of rTMS to lDLPFC on any hypnotic measure. Our second experiment used rTMS applied to right rather then left DLPFC. This right-sided stimulation enhanced hypnotizability (when hypnotic response was measured objectively), as predicted by our hypothesis. These results imply a role for rDLPFC in the cognitive process of belief evaluation, as is proposed in our two-factor theory of delusion. They are also consistent with a conception of the acceptance of a hypnotic suggestion as involving suspension of disbelief.

Indirect task instructions better reveal theory-of-mind impairment, independent of executive dysfunction, in schizophrenia.

Theory of mind (TOM) impairments associate significantly with executive deficits in schizophrenia, consistent with the proposal that executive abilities can limit TOM task performance, and confounding identification of those patients who would benefit most from targeted mentalising interventions. 50 schizophrenia patients and 30 healthy controls completed an executive battery and four TOM tasks that were alike with regards generating overt measures of causal false-belief reasoning, but differed with regards using indirect (vs. more direct) instructions. Only the TOM tasks that used indirect instructions to elicit spontaneous false-belief inferences revealed impairment, independent of executive dysfunction, in the schizophrenia patients.

The Fregoli delusion: a disorder of person identification and tracking.

Fregoli delusion is the mistaken belief that some person currently present in the deluded person's environment (typically a stranger) is a familiar person in disguise. The stranger is believed to be psychologically identical to this known person (who is not present) even though the deluded person perceives the physical appearance of the stranger as being different from the known person's typical appearance. To gain a deeper understanding of this contradictory error in the normal system for tracking and identifying known persons, we conducted a detailed survey of all the Fregoli cases reported in the literature since the seminal Courbon and Fail (1927) paper. Our preliminary reading of these cases revealed a notable lack of definitional clarity. So, we first formulated a classification scheme of different person misidentification delusions so as to identify those cases that qualified as instances of Fregoli according to the above characterization: the mistaken belief that a known person is present in the environment in a different guise to his or her typical appearance. We identified 38 clear cases of this type and set out to answer a series of questions motivated by current hypotheses about the origin of the Fregoli delusion. We asked whether the patients misidentified particular strangers, made reference to the misidentified known persons using wigs or plastic surgery (or other techniques to disguise their appearance), misidentified many different strangers or only one, showed other symptoms (in particular, other misidentification delusions), and made inferences about the motives of the known persons in disguise. We conclude by discussing the implications of our findings for current hypotheses concerning the origin of the Fregoli delusion.

Social cognition and social judgment in schizophrenia.

Schizophrenia typically involves poor social functioning. This may be due, in part, to deficits in theory-of-mind, the cognitive ability to reason flexibly about the mental states of others. Patients also have deficits in social knowledge. It is currently unclear how these two impairments interrelate in schizophrenia. To address this issue, 43 patients with schizophrenia and 25 healthy controls completed two theory-of-mind tests and a novel test of social judgment. This latter measure required participants to judge whether various social behaviors were normal or reasonable in the context in which the behaviors occurred. Whereas patients demonstrated clear deficits in theory-of-mind, they performed similarly to controls when judging socially appropriate behaviors and violations of social norms. Patients, however, were less likely than controls to judge social behavior as reasonable when the behavior was impolite but understandable if the characters' thoughts were taken into account. This latter difficulty correlated with patients' performance deficits on the theory-of-mind tasks. Overall, findings suggest that basic social knowledge is intact in schizophrenia, though judgments of social behavior are affected by patients' theory-of-mind deficits.