Abstract
Background:Wernicke’s concept of ‘sejunction’ or aberrant associations among specialized brain regions is one of the earliest hypotheses attempting to explain the myriad of symptoms in psychotic disorders. Unbiased data mining of all possible brain-wide connections in large data sets is an essential first step in localizing these aberrant circuits.Methods:We analyzed functional connectivity using the largest resting-state neuroimaging data set reported to date in the schizophrenia literature (415 patients vs. 405 controls from UK, USA, Taiwan, and China). An exhaustive brain-wide association study at both regional and voxel-based levels enabled a continuous data-driven discovery of the key aberrant circuits in schizophrenia.Results:Results identify the thalamus as the key hub for altered functional networks in patients. Increased thalamus–primary somatosensory cortex connectivity was the most significant aberration in schizophrenia (P=10−18). Overall, a number of thalamic links with motor and sensory cortical regions showed increased connectivity in schizophrenia, whereas thalamo–frontal connectivity was weakened. Network changes were correlated with symptom severity and illness duration, and support vector machine analysis revealed discrimination accuracies of 73.53–80.92%.Conclusions:Widespread alterations in resting-state thalamocortical functional connectivity is likely to be a core feature of schizophrenia that contributes to the extensive sensory, motor, cognitive, and emotional impairments in this disorder. Changes in this schizophrenia-associated network could be a reliable mechanistic index to discriminate patients from healthy controls.
Highlights
One of the earliest mechanistic notions proposed to account for the myriad of symptoms seen in individuals with psychotic disorders is the concept of ‘sejunction’ put forward by Wernicke in 1894.1 Wernicke believed that a disjunction between distinct functional modules that involve both sensorimotor and association areas of the brain generate symptoms of psychosis.[2]
We investigate clinical associations among the so-called ‘sejunction circuitry’, symptom severity, and illness duration, and the extent to which it can reliably discriminate between patients and controls using a pattern classification approach
The most significantly altered cluster was in the thalamus (Figure 1a: Peak Montreal Neurological Institute coordinate (−12, − 18, 6), cluster size 442, measure for the association (MA) 222) and involved 5,620 links, while the second most significantly altered cluster was in the postcentral gyrus (Peak Montreal Neurological Institute coordinate (−48, − 27, 42), cluster size 167, MA 61) and involved 1,045 links
Summary
Wernicke’s concept of ‘sejunction’ or aberrant associations among specialized brain regions is one of the earliest hypotheses attempting to explain the myriad of symptoms in psychotic disorders. METHODS: We analyzed functional connectivity using the largest resting-state neuroimaging data set reported to date in the schizophrenia literature (415 patients vs 405 controls from UK, USA, Taiwan, and China). An exhaustive brain-wide association study at both regional and voxel-based levels enabled a continuous data-driven discovery of the key aberrant circuits in schizophrenia. CONCLUSIONS: Widespread alterations in resting-state thalamocortical functional connectivity is likely to be a core feature of schizophrenia that contributes to the extensive sensory, motor, cognitive, and emotional impairments in this disorder. Changes in this schizophrenia-associated network could be a reliable mechanistic index to discriminate patients from healthy controls. Npj Schizophrenia (2015) 1, Article number: 15016; doi:10.1038/npjschz.2015.16; published online 6 May 2015
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
