The relationship between regional and inter-regional functional connectivity deficits in schizophrenia.

While schizophrenia is frequently characterized as a disorder of disturbed functional connectivity, the causes and pathophysiological origins of such disturbances remain unclear. The aim of this study was to better elucidate the mechanistic causes of abnormal functional connectivity in schizophrenia, measured as the extent of temporal correlation between endogenous fluctuations recorded at anatomically discrete brain regions during resting-state functional MRI. An approach was developed to perform whole-brain connectivity mapping at the resolution of individual pairs of voxels, without the need for arbitrary parcellation of the cerebrum. Between-group connectivity reductions in 12 people diagnosed with schizophrenia and 15 age-, IQ-, and gender-matched healthy volunteers were localized to a distributed network including frontoparietal and occipitoparietal connections. The gray-matter regions comprising this disturbed network showed evidence of local reductions in both intra-regional homogeneity (29%-33% reduction) and signal power (40%-60% reduction). The extent to which inter-regional correlation was reduced between a pair of gray matter regions was found to be strongly correlated with the extent of local decoherence evident within the gray matter regions per se. This suggests measurement of aberrant functional connectivity in schizophrenia is both a measurement of altered coupling between regions as well as a measurement of local decoherence within regions.