Disruption of structure–function coupling in the schizophrenia connectome

Abstract

Neuroimaging studies have demonstrated that the phenomenology of schizophrenia maps onto diffuse alterations in large-scale functional and structural brain networks. However, the relationship between structural and functional deficits remains unclear. To answer this question, patients with established schizophrenia and matched healthy controls underwent resting-state functional and diffusion weighted imaging. The network-based statistic was used to characterize between-group differences in whole-brain functional connectivity. Indices of white matter integrity were then estimated to assess the structural correlates of the functional alterations observed in patients. Finally, group differences in the relationship between indices of functional and structural brain connectivity were determined. Compared to controls, patients with schizophrenia showed decreased functional connectivity and impaired white matter integrity in a distributed network encompassing frontal, temporal, thalamic, and striatal regions. In controls, strong interregional coupling in neural activity was associated with well-myelinated white matter pathways in this network. This correspondence between structure and function appeared to be absent in patients with schizophrenia. In two additional disrupted functional networks, encompassing parietal, occipital, and temporal cortices, the relationship between function and structure was not affected. Overall, results from this study highlight the importance of considering not only the separable impact of functional and structural connectivity deficits on the pathoaetiology of schizophrenia, but also the implications of the complex nature of their interaction. More specifically, our findings support the core nature of fronto-striatal, fronto-thalamic, and fronto-temporal abnormalities in the schizophrenia connectome.

Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation

“…Such deficits have been consistently associated with altered lateral prefrontal activity (Tan et al, 2005). In line with these results, recent resting-state fMRI investigations have shown that symptoms of schizophrenia involve widespread hypo-connectivity between frontal areas and temporal, thalamic, and striatal regions Anticevic et al, 2015;Cocchi et al, 2014; van den Heuvel M a n u s c r i p t Sale et al,30 and Fornito, 2014). This hypoconnectivity has often been associated with an early dysregulation in the function of frontal circuitry (Anticevic et al, 2015).…”

“…Likewise, reduced beta-and gamma-synchrony between distal cortical regions is thought to play a key role in the pathophysiology of schizophrenia (Uhlhaas and Singer, 2010). Given that tACS can selectively boost the power of neural oscillations at specific frequencies between stimulated regions (Helfrich et al, 2014), such approaches might be used to enhance the power of these oscillations in schizophrenia, thereby strengthening the coupling of neural activity between targeted brain regions Cocchi et al, 2014) (Fig. 4).…”

Theta response in schizophrenia is indifferent to perceptual illusion

“…T. Bates, et al, 2009). Recent studies have further shown that specifically long-range connections of the frontal cortex are disturbed in schizophrenia (Cocchi et al, 2014;Fornito, Zalesky, Pantelis, & Bullmore, 2012). Disturbances of theta activity in schizophrenia might, therefore, be an indicator of dysfunctional mechanisms in temporal and regional coordination (Andreasen, 2000;Basar-Eroglu, et al, 2008;Basar-Eroglu, et al, 2009;Friston & Frith, 1995;Winterer et al, 2000).…”

Cerebral cartography and connectomics

“…in disruptions of highly central nodes or edges [134,135]. Disturbed structure/function relationships have been detected in schizophrenia [136], and disruptions of both structural and functional connectivity appear to be associated with different neurodegenerative conditions [137]. These clinical findings reinforce the need for cerebral cartography to capture not only normative patterns or population averages but also individual differences in brain connectivity.…”