Neurocognitive bases of self-monitoring of inner speech in hallucination prone individuals

Verbal hallucinations in schizophrenia patients might be seen as internal verbal productions mistaken for perceptions as a result of over-salient inner speech and/or defective self-monitoring processes. Similar cognitive mechanisms might underpin verbal hallucination proneness in the general population. We investigated, in a non-clinical sample, the cerebral activity associated with verbal hallucinatory predisposition during false recognition of familiar words —assumed to stem from poor monitoring of inner speech—vs. uncommon words. Thirty-seven healthy participants underwent a verbal recognition task. High- and low-frequency words were presented outside the scanner. In the scanner, the participants were then required to recognize the target words among equivalent distractors. Results showed that verbal hallucination proneness was associated with higher rates of false recognition of high-frequency words. It was further associated with activation of language and decisional brain areas during false recognitions of low-, but not high-, frequency words, and with activation of a recollective brain area during correct recognitions of low-, but not high-, frequency words. The increased tendency to report familiar words as targets, along with a lack of activation of the language, recollective, and decisional brain areas necessary for their judgement, suggests failure in the self-monitoring of inner speech in verbal hallucination-prone individuals

An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol

Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH. Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021)

Remembering verbally-presented items as pictures:brain activity underlying visual mental images in schizophrenia patients with visual hallucinations

Background: Previous research suggests that visual hallucinations in schizophrenia consist of mental images mistaken for percepts due to failure of the reality-monitoring processes. However, the neural substrates that underpin such dysfunction are currently unknown. We conducted a brain imaging study to investigate the role of visual mental imagery in visual hallucinations. Method: Twenty-three patients with schizophrenia and 26 healthy participants were administered a reality-monitoring task whilst undergoing an fMRI protocol. At the encoding phase, a mixture of pictures of common items and labels designating common items were presented. On the memory test, participants were requested to remember whether a picture of the item had been presented or merely its label. Results: Visual hallucination scores were associated with a liberal response bias reflecting propensity to erroneously remember pictures of the items that had in fact been presented as words. At encoding, patients with visual hallucinations differentially activated the right fusiform gyrus when processing the words they later remembered as pictures, which suggests the formation of visual mental images. On the memory test, the whole patient group activated the anterior cingulate and medial superior frontal gyrus when falsely remembering pictures. However, no differential activation was observed in patients with visual hallucinations, whereas in the healthy sample, the production of visual mental images at encoding led to greater activation of a fronto-parietal decisional network on the memory test. Conclusions: Visual hallucinations are associated with enhanced visual imagery and possibly with a failure of the reality-monitoring processes that enable discrimination between imagined and perceived events

Neural activity during object perception in schizophrenia patients is associated with illness duration and affective symptoms

Background - Abnormalities in visual processes have been observed in schizophrenia patients and have been associated with alteration of the lateral occipital complex and visual cortex. However, the relationship of these abnormalities with clinical symptomatology is largely unknown. Methods - We investigated the brain activity associated with object perception in schizophrenia. Pictures of common objects were presented to 26 healthy participants (age = 36.9; 11 females) and 20 schizophrenia patients (age = 39.9; 8 females) in an fMRI study. Results - In the healthy sample the presentation of pictures yielded significant activation (pFWE (cluster) < 0.001) of the bilateral fusiform gyrus, bilateral lingual gyrus, and bilateral middle occipital gyrus. In patients, the bilateral fusiform gyrus and bilateral lingual gyrus were significantly activated (pFWE (cluster) < 0.001), but not so the middle occipital gyrus. However, significant bilateral activation of the middle occipital gyrus (pFWE (cluster) < 0.05) was revealed when illness duration was controlled for. Depression was significantly associated with increased activation, and anxiety with decreased activation, of the right middle occipital gyrus and several other brain areas in the patient group. No association with positive or negative symptoms was revealed. Conclusions - Illness duration accounts for the weak activation of the middle occipital gyrus in patients during picture presentation. Affective symptoms, but not positive or negative symptoms, influence the activation of the right middle occipital gyrus and other brain areas

A large-scale study on the effects of sex on gray matter asymmetry

Research on sex-related brain asymmetries has not yielded consistent results. Despite its importance to further understanding of normal brain development and mental disorders, the field remains relatively unexplored. Here we employ a recently developed asymmetry measure, based on the Dice coefficient, to detect sex-related gray matter asymmetries in a sample of 457 healthy participants (266 men and 191 women) obtained from 5 independent databases. Results show that women’s brains are more globally symmetric than men’s (p < 0.001). Although the new measure accounts for asymmetries distributed all over the brain, several specific structures were identified as systematically more symmetric in women, such as the thalamus and the cerebellum, among other structures, some of which are typically involved in language production. These sex-related asymmetry differences may be defined at the neurodevelopmental stage and could be associated with functional and cognitive sex differences, as well as with proneness to develop a mental disorder

Pattern of severe injuries in Spanish children: boys and falls are alarmingly overrepresented

ABSTRACTBackground: Taking into account that injury is one of the main causes of child fatalities in developed countries, and that boys are more likely to suffer it than girls, we have explored a database of pediatric patients with severe injuries to determine whether sex and age influence the pattern of these fatalities, and the magnitude of this.Method: Observational study of the demographic and clinical characteristics of 227 patients from a Spanish pediatric reference hospital, all of them admitted with a diagnosis of trauma.Result: Falls are the most frequent type of trauma (60.7%), followed by pedestrian traffic collisions (15%). Boys are over-represented in falls (72% vs 28% in girls) and pedestrian traffic injuries (61% vs 39 %). In boys, falls are mainly observed in public roads and during leisure activities (53.8%) whereas in girls at home (55.2%). In a logistic regression, sex and age are statistically significant predictors of severe trauma, boys (OR = 1.59) and the adolescent age group (OR = 3.7) showed the highest odds.Conclusion: We have observed a clear gender-biased pattern of injury-related events: falls are the leading cause of injuries, with 2.5 boys for every girl. Falls mostly happened during outdoor leisure activities in boys and at home in girls. Pedestrian traffic injuries also show significant differences between sexes, emphasizing the role of cognitive and cultural factors in children’s behavior.</jats:p