The noise in our brain: A systematic review and meta-analysis of neuroimaging and signal-detection studies on source monitoring in psychosis.

OBJECTIVES: Noisy thoughts or perceptions are characteristics of psychosis (PSY) and, they are deeply related to source monitoring (SM) - the ability to discriminate the origin of internal/external experiences. METHODS: This MOOSE, PRISMA-compliant meta-analysis compared SM performances in PSY compared to healthy controls (HC) focusing on signal-to-noise discrimination in order to: i) test whether neuroimaging procedures (fMRI/EEG) might be a group-specific source of noise for SM; ii) compare error- and accuracy-based indexes; iii) to meta-analyze signal-detection measures (i.e., discrimination index and response bias); iv) to determine the best index capturing SM deficits in psychosis. We conducted a 3-level meta-analysis for each aim to estimate pooled effect-sizes (Cohen's d). SM type, source discrimination and stimulus modality were used as meta-regressors. Heterogeneity (I2), publication bias (Egger's test) and multiple comparisons (Bonferroni correction) were considered. RESULTS: Sixteen neuroimaging, 44 error/accuracy-based behavioral and 7 signal-detection trials were included (2297 PSY, age range = 18.78-52.6; 1745 HC, age range = 21.1-53.3). The noise generated by neuroimaging procedures slightly influenced error, but not accuracy. Accuracy-based (d = -0.83), but not error-based, indexes showed significant and large SM impairments in PSY compared to HC. Overall SM performance differences between PSY and HC were larger in discrimination index (d = -0.65) and accuracy (d = -0.61), followed by response bias (d = -0.59, ns) and error-based (d = 0.35) indexes. CONCLUSION: Although both accuracy and discrimination indexes differentiate patients with PSY from HC, discrimination index is more reliable and may better capture the bi-directional nature of the internal/external source confusion.

Self-reported interoception and exteroception are atypical and excessively coupled in psychosis compared to healthy controls.

Although psychotic disorders are characterized by an impaired ability to discriminate internal and external worlds, the role of interoceptive and exteroceptive perceptions in determining this alteration is still unclear. This observational study aimed at investigating (a) increases/decreases in interoceptive and exteroceptive perceptions in patients with psychosis (PSY) compared to healthy controls (HC); (b) the association between interoception and exteroception in HC and PSY. Two hundred and ten HC and 72 PSY completed the Multidimensional Assessment of Interoceptive awareness (MAIA, 8 domains) and the Adolescent-Adult Sensory Profile (AASP, 4 domains). MAIA/AASP differences were evaluated with MANOVA, Kruskal-Wallis and Mann-Whitney tests. MAIA and AASP scores were correlated to quantify the interoceptive-exteroceptive coupling as Spearman's rho coefficients. Subgroup analyses were performed dividing PSY in schizophrenia/schizoaffective versus other psychosis. Compared to HC, PSY showed increased mean scores in four MAIA and two AASP domains (Bonferroni-p < 0.01). The interoceptive-exteroceptive coupling followed two correlation patterns in HC. A first pattern displayed negative correlations between MAIA not-worrying and AASP sensory sensitivity/sensation avoidance, while the second pattern highlighted positive correlations between MAIA scores and AASP sensation seeking. The two correlation patterns between HC and other-PSY subgroup were similar. However, schizophrenia/schizoaffective PSY did not show positive correlations in the second pattern, rather displaying negative correlations between MAIA scores and AASP domains related to passive behavioral responses. Correlation values were more extreme in PSY subgroups, indicating stronger interoceptive-exteroceptive coupling compared to HC. This study demonstrates that interoception and exteroception are atypical and excessively coupled in psychosis compared to the general population.Clinical Trials Registration: Protocol Number 20210003663 (Pavia, Ethical Committee IRCCS Policlinico San Matteo).

Understanding source monitoring subtypes and their relation to psychosis: a systematic review and meta-analysis.

AIMS: Source monitoring (SM) is the metacognitive ability to determine the origin of one's experiences. SM is altered in primary psychiatric psychosis, although relationships between SM subtypes, other cognitive domains and symptoms are unclear. Our aims were to synthesize evidence comparing psychosis -with and without hallucinations- and healthy controls classifying SM subtypes by source discrimination (internal/external/reality monitoring) and stimulus modality (visual/auditory/imagined/performed). METHODS: This systematic review adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Meta-analyses Of Observational Studies in Epidemiology and Population, Intervention, Comparison and Outcomes guidelines. Core demographical and clinical parameters were extracted. Newcastle-Ottawa Scale was used as quality check. SM differences between (i) psychosis patients versus healthy controls and (ii) patients with versus without hallucinations were investigated via random-effect model meta-analysis. The primary effect size measure was standardized mean difference (SMD) in each SM subtype performance (error or accuracy). Heterogeneity, publication biases and meta-regressions were assessed. RESULTS: Five thousand two hundred and fifty-six records were screened to finally include 44 studies (1566 patients, 1175 controls). Mean Newcastle-Ottawa score was 7.41 out of 9. Few studies measured SM associations with cognition (n = 9) and symptoms (n = 19), with heterogeneous findings. SM performance across all measures was reduced in psychosis versus healthy controls (SMD = 0.458). Internal SM (SMD: errors = 0.513; accuracy = 0.733) and imagined stimuli (SMD: errors = 0.688; accuracy = 0.978) were specifically impaired. Patients with versus without hallucinations showed SM deficits only for externalizing (SMD = 0.410) and imagined/auditory (SMD = 0.498/0.277) errors. CONCLUSION: The proposed classifications highlight specific SM deficits for internal/imagined stimuli in psychosis, providing evidence-based indications to design and interpret future studies.

Effectiveness and safety of intravenous valproate in agitation: a systematic review.

RATIONALE: The use of intravenous valproate is not approved for clinical practice in psychiatry. Literature data pointed out for a potential usefulness of this route of administration for valproate, but there is no actual consensus. OBJECTIVES: The aim of the present systematic review is to assess the effectiveness of intravenous valproate in agitation as well as general safety. METHODS: A systematic review of studies evaluating the use of intravenous valproate in agitation was conducted. Additionally, safety was evaluated in all randomized trials involving the use of intravenous valproate in all medical conditions (epilepsy, migraine and psychiatric conditions). RESULTS: For the systematic review on effectiveness in agitation, the search yielded 965 articles overall. After removing duplicates, 9411 articles were screened by title and abstract, and 39 of these were evaluated at a full-text level. Six studies were considered eligible for qualitative synthesis: one RCT and case report (n = 3), followed by cohort studies (n = 2). For the systematic review on safety, twenty-two RCTs were considered eligible for quantitative synthesis. CONCLUSION: Intravenous valproate seems efficacious in reducing agitation in psychiatric patients; it generally appears safe compared to other neuroleptics or antiepileptics. However, the evidence is still not strong as it  relies mainly on open-label studies or case series.

Two Faces of a Coin? A Systematic Review of Source Monitoring and Its Relationship with Memory in Autism.

The ability to discriminate the origin of stimuli, known as source monitoring, is crucial for self-other distinction and the integration of internally generated and externally generated experiences. Despite its valence, evidence on source monitoring in autism is yet scarce and unclear. We systematically reviewed literature concerning source monitoring in autism and its relationship with other constructs, such as memory type, encoding effects, social cognition, general intelligence, and clinical factors. Source-monitoring performance (operationalized as error or accuracy) was reduced in autistic participants in 9 of the 15 studies that met the inclusion criteria. When explicitly investigated, free-recall memory impairments in autism were shown to influence source monitoring deficits. General intelligence was another important factor linked to source-monitoring performance. Conversely, other memory types or encoding effects were not impaired in autism, and no univocal association could be found with source monitoring. Social cognition and clinical symptoms were rarely assessed in spite of their possible involvement in source monitoring. The heterogeneity of the task design, outcome measures and demographical factors limited study comparability. As a research framework on source monitoring as a construct of primary interest in autism is still lacking, we propose preliminary indications for future investigations based on the collected findings.