BACKGROUND
The Fusiform Gyrus (FG), a brain region relevant for the interaction between cognitive processes and emotional behavior, especially emotion recognition and interpretation of social cues, has been linked to the pathophysiology of schizophrenia conceptualized as a disorder of aberrant synaptic function and brain connectivity as well as characterized by disruptions in thought processes, perceptions, emotional responsiveness, and Theory of Mind (ToM). Disrupted FG connectivity has been reported in schizophrenia; however, no systematic review has addressed this issue in a comprehensive and critical manner.
METHODS
We conducted a systematic review of PubMed, Embase, and Scopus from database inception to February 2026 following PRISMA guidelines. We included peer-reviewed neuroimaging studies using functional magnetic resonance imaging to assess functional connectivity or task-related activation of the FG in patients with schizophrenia compared with healthy controls.
RESULTS
We identified 2765 articles from different sources. After duplicate removal, 959 articles were screened at the title-abstract level, 269 articles were reviewed for full-texts, and 86 eligible articles were included. Across fMRI studies, the FG emerged as a central node of dysconnectivity. Drug-naïve patients showed heterogeneous FG alterations, with increased local activity and network centrality reported in some studies and reduced interhemispheric and functional connectivity in others, alongside reduced FG activation on visual, affective, and sensory tasks reported more broadly across schizophrenia samples. First-episode psychosis patients were characterized by FG hypoconnectivity associated with negative symptoms and socio-cognitive impairment. Treatment-responsive patients demonstrated partial normalization or modulation of fusiform connectivity and network centrality following antipsychotic treatment. In contrast, treatment-resistant schizophrenia patients showed persistent hypoactivation and reduced connectivity, correlating with cognitive deficits and negative symptoms.
CONCLUSIONS
The FG appears to function as a dynamic, state-sensitive hub underlying perceptual, emotional, and cognitive disturbances in schizophrenia, in line with impaired ToM.
M. Ciccarelli, B. Mazza, A. Nasti et al.· Neuroscience and Biobehavior...· 0 citations
Abstract Background Recent evidence supports the hypothesis that schizophrenia is part of a continuum of neurodevelopmental disorders (NDDs), characterized by early alterations in fronto-striatal, parietal, and cerebellar circuits (Owen, 2017). In this perspective, Autism Spectrum Disorder Level 1 (ASD-L1) and schizophrenia share genetic and neurocognitive vulnerabilities, particularly in the domains of executive functions (EF), such as sustained attention, working memory, and perseveration. Comparative studies have highlighted a wide overlap in the cognitive profiles of adults with ASD-L1 and patients with schizophrenia (Morais et al., 2024; Yon-Hernández et al., 2023). Furthermore, these deficits are also observable in subjects at high clinical risk for psychosis (Fusar-Poli et al., 2012), supporting the hypothesis that some executive deficits represent shared cognitive vulnerability markers among various neurodevelopmental disorders. The use of virtual reality (VR) tools for EF assessment offers an ecologically valid approach, which is sensitive to the dynamic components of cognitive functioning and particularly suitable for the assessment of subjects with complex cognitive profiles, such as those observed in neurodevelopmental disorders. Aims & Objectives To explore the profile of executive functions in a sample of adults with ASD-L1 using virtual reality tools, and to evaluate its convergence with the cognitive patterns described in schizophrenia and clinical high-risk states for psychosis. Method 24 adults diagnosed with ASD-L1 (DSM-5; 17 males, 7 females; mean age: 26 years) and 21 healthy controls matched for age and sex were evaluated. Executive Functions were investigated using the NESPLORA virtual reality software, across the following domains: sustained attention, working memory, flexibility, perseveration, inhibition, vigilance, and planning. Performance was classified into ordinal categories (normal, low, very low). Descriptive analyses and association tests (chi-square test ; Fisher's exact test) were conducted using R Studio (version 4.2). Results The most compromised domains in the sample of adults with ASD-L1 were: attention (60% with low/very low performance), working memory (54%), and perseveration (52%). Significant associations emerged between attention and working memory (p = 0.0007), and between working memory and perseveration (p = 0.032). Using Fisher's exact test, a statistically significant difference was observed between the two groups (patients and controls) in the proportion of subjects showing deficits in attention (p-value = 0.01795) and perseveration (p-value = 0.0001648). Discussion & Conclusions The observed pattern of impairment is consistent with that described in chronic schizophrenia and clinical high-risk states for psychosis (Engel & Karch, 2023), confirming that these domains are frequently altered along the continuum of Neurodevelopmental Syndromes (NDS). Comparative studies indicate that adults with ASD-L1 and SCZ patients show overlapping performance in executive functions, confirming a sharing of cognitive vulnerabilities (Eack et al., 2013; Yon-Hernández et al., 2023). Ongoing analyses of effect magnitude will contribute to a more precise understanding of their clinical relevance. The use of virtual reality proved to be a highly sensitive tool suitable for the assessment of these profiles, providing dynamic and contextualized measures of executive functioning. These results open interesting perspectives for the development of early and personalized interventions in NDDs, with potential implications for transdiagnostic and prevention fields.
C. Ceparano, F. Iannotta, C. Ricci et al.· International Journal of Neu...· 0 citations
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