Reduced functional connectivity during controlled semantic integration in schizophrenia: A multivariate approach.

Impairment in controlled semantic association is a central feature of schizophrenia, and the goal of the current functional magnetic resonance imaging study was to identify the neural correlates of this impairment. Thirty people with schizophrenia and 30 healthy age- and gender-matched control subjects performed a task requiring participants to match word pairs that varied in semantic distance (distant vs. close). A whole-brain multivariate connectivity analysis revealed three functional brain networks of primary interest engaged by the task: two configurations of a multiple demands network, in which brain activity did not differ between groups, and a semantic integration network, in which coordinated activity was reduced in schizophrenia patients relative to healthy controls, for distantly relative to closely related word pairs. The hypoactivity during controlled semantic integration in schizophrenia reported here, combined with hyperactivity in automatic semantic association reported in the literature, suggests an imbalance between controlled integration and automatic association. This provides a biological basis for Bleuler's concept of schizophrenia as a "split mind" arising from an impaired ability to form coherent associations between semantic concepts.