Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia.
COBISS.SI-ID: 55254626
Schizophrenia is a devastating neuropsychiatric syndrome associated with distributed brain dysconnectivity that may involve large-scale thalamo-cortical systems. Incomplete characterization of thalamic connectivity in schizophrenia limits our understanding of its relationship to symptoms and to diagnoses with shared clinical presentation, such as bipolar illness, which may exist on a spectrum. Using resting-state functional magnetic resonance imaging, we characterized thalamic connectivity in 90 schizophrenia patients versus 90 matched controls via: (1) Subject-specific anatomically defined thalamic seeds; (2) anatomical and data-driven clustering to assay within-thalamus dysconnectivity; and (3) machine learning to classify diagnostic membership via thalamic connectivity for schizophrenia and for 47 bipolar patients and 47 matched controls. Schizophrenia analyses revealed functionally related disturbances: Thalamic over-connectivity with bilateral sensory-motor cortices, which predicted symptoms, but thalamic under-connectivity with prefrontal-striatal-cerebellar regions relative to controls, possibly reflective of sensory gating and top-down control disturbances. Clustering revealed that this dysconnectivity was prominent for thalamic nuclei densely connected with the prefrontal cortex. Classification and cross-diagnostic results suggest that thalamic dysconnectivity may be a neural marker for disturbances across diagnoses. Present findings, using one of the largest schizophrenia and bipolar neuroimaging samples to date, inform basic understanding of large-scale thalamo-cortical systems and provide vital clues about the complex nature of its disturbances in severe mental illness.
COBISS.SI-ID: 52467554
Empirical and theoretical studies implicate thalamocortical circuits in schizophrenia, supported by emerging restingstate functional connectivity studies (rs-fcMRI). Similar but attenuated alterations were found in bipolar disorder (BD). However, it remains unknown if segregated loops within thalamocortical systems show distinct rs-fcMRI alterations in schizophrenia. For instance, the mediodorsal (MD) nucleus, known to project to prefrontal networks, may be differently altered than the lateral geniculate nucleus (LGN), known to project to the occipital cortex. Also, it remains unknown if these circuits show different patterns of alterations in BD as a function of psychosis history, which may be associated with a more severe clinical course. We addressed these questions in 90 patients with chronic schizophrenia and 73 remitted BD patients (33 with psychosis history) matched to 146 healthy comparison subjects. We hypothesized that the MD vs LGN would show dissociations across diagnostic groups. We found that MD and LGN show more qualitative similarities than differences in their patterns of dysconnectivity in schizophrenia. In BD, patterns qualitatively diverged between thalamic nuclei although these effects were modest statistically. BD with psychosis history was associated with more severe dysconnectivity, particularly for the MD nucleus. Also, the MD nucleus showed connectivity reductions with the cerebellum in schizophrenia but not in BD. Results suggest dissociations for thalamic nuclei across diagnoses, albeit carefully controlling for medication is warranted in future studies. Collectively, these findings have implications for designing more precise neuroimagingdriven biomarkers that can identify common and divergent large-scale network perturbations across psychiatric diagnoses with shared symptoms.
COBISS.SI-ID: 55252834