Disrupted Axonal Fiber Connectivity in Schizophrenia

Abstract

Background Schizophrenia is believed to result from abnormal functional integration of neural processes thought to arise from aberrant brain connectivity. However, evidence for anatomical dysconnectivity has been equivocal, and few studies have examined axonal fiber connectivity in schizophrenia at the level of whole-brain networks. Methods Cortico-cortical anatomical connectivity at the scale of axonal fiber bundles was modeled as a network. Eighty-two network nodes demarcated functionally specific cortical regions. Sixty-four direction diffusion tensor-imaging coupled with whole-brain tractography was performed to map the architecture via which network nodes were interconnected in each of 74 patients with schizophrenia and 32 age- and gender-matched control subjects. Testing was performed to identify pairs of nodes between which connectivity was impaired in the patient group. The connectional architecture of patients was tested for changes in five network attributes: nodal degree, small-worldness, efficiency, path length, and clustering. Results Impaired connectivity in the patient group was found to involve a distributed network of nodes comprising medial frontal, parietal/occipital, and the left temporal lobe. Although small-world attributes were conserved in schizophrenia, the cortex was interconnected more sparsely and up to 20% less efficiently in patients. Intellectual performance was found to be associated with brain efficiency in control subjects but not in patients. Conclusions This study presents evidence of widespread dysconnectivity in white-matter connectional architecture in a large sample of patients with schizophrenia. When considered from the perspective of recent evidence for impaired synaptic plasticity, this study points to a multifaceted pathophysiology in schizophrenia encompassing axonal as well as putative synaptic mechanisms.

Emerging Evidence of Connectomic Abnormalities in Schizophrenia

“…The only other comparable study was published almost simultaneously by Zalesky et al (2011). Unlike van den Heuvel et al (2010), Zalesky et al (2011) report global reductions in whitematter connectivity, rather than more subtle regional changes in connectivity.…”

“…The only other comparable study was published almost simultaneously by Zalesky et al (2011). Unlike van den Heuvel et al (2010), Zalesky et al (2011) report global reductions in whitematter connectivity, rather than more subtle regional changes in connectivity. While these reported differences may arise from the relatively small sample size in both studies and the heterogeneity of neuropathology in schizophrenia, it is also worth mentioning an important methodological difference between the two studies.…”

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

“…Many of the most common psychiatric conditions are now known to involve brain network dysfunction, including schizophrenia, autism spectrum disorders, depression and obsessive compulsive disorder (OCD) (Insel, 2010;Zalesky et al, 2011;Cocchi et al, 2012;Fornito et al, 2012). Studies of the human connectome have provided a means to delineate subtypes of psychiatric disorders based upon neurobiology, to characterize the neural basis of specific symptoms, and to monitor the brain's response to treatment, as well as defining neural markers of illness (Filippi et al, 2013;Fornito et al, 2015).…”

Disrupted Global and Regional Structural Networks and Subnetworks in Children with Localization-Related Epilepsy

“…Finally, a nonparametric permutation test (10,000 permutations) and a secondary threshold of P ϭ .05 were used to choose the significant components. [24][25][26] This method effectively controls for false-positives due to multiple comparisons.…”