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
PURPOSE
Corticobasal syndrome (CBS) is a clinically defined phenotype with different underlying neuropathological substrates most commonly the 4-repeat tauopathy corticobasal degeneration (CBD). 2-[18F] fluoro-2-deoxy-D-glucose Positron Emission Tomography ([18F]FDG-PET) studies have described regional metabolic abnormalities but detailed subcortical and cerebellar structures involvement is less known and metabolic connectivity remains unexplored. This study combined voxel-based, region-of-interest (ROI) analyses and connectivity approaches to further characterize metabolic alterations and to provide a network-level framework in CBS.
METHODS
Thirty-nine CBS patients underwent [18F]FDG-PET at two sites, with images flipped to align the most affected hemisphere; 99 controls were drawn from a national normative database. Voxel-based SPM method and ROIs analysis were performed. Thirty-six bilateral cortical and subcortical regions of interest were processed to perform interregional correlation and network-based analyses within five functional networks. Pairwise Spearman correlations were computed from normalized regional signals. Group differences were assessed at regional and network levels using Fisher-transformed correlations, Cohen's q, permutation testing (10,000 iterations), and graph-theoretical metrics (node strength, clustering coefficient; threshold ρ > 0.25).
RESULTS
CBS patients showed asymmetric hypometabolism predominantly in frontal, parietal, and temporal cortices, caudate and thalamus of the predominantly affected hemisphere, with additional contralateral involvement, notably in the cerebellum and caudate. Metabolic connectivity analyses revealed widespread intra- and inter-network disconnection, particularly involving frontal, parietal, and sensorimotor cortices, and thalamo-cortical pathways, with significant lateralization toward the affected hemisphere. Graph analysis showed decreased cortical node strength with relative increases in subcortical hubs and mixed changes in clustering coefficients, suggesting network reorganization.
CONCLUSION
This first [18F]FDG-PET metabolic connectivity study in CBS demonstrates asymmetric and bilateral regional hypometabolism, widespread and lateralized network disconnection, and subcortical reorganization. These findings reflect both degenerative, functional and compensatory mechanisms and highlight metabolic connectivity as a sensitive marker of network-level alterations in neurodegenerative disease.
Matilde Nerattini, A. Leo, Valentina Bessi et al.· European Journal of Nuclear...· 0 citations
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