General and specific functional connectivity disturbances in first-episode schizophrenia during cognitive control performance.

Schematic overview of the analysis strategy. The analysis could be divided into four broad steps. First, a unique regressor was generated for every event, and event-specific evoked responses were estimated using a general linear model. The result was a map of β coefficients for each event, representing the degree to which each voxel’s activity was modulated by that event. Second, these event-specific β maps were sorted into different task conditions (cue A shown in blue, cue B show in red) and concatenated to generate a condition-specific pseudo–time series of β coefficients (i.e., a β series) at each voxel. Third, an anatomic template was used to parcellate the brain in 78 regions. The mean β series of each region was extracted, and correlations between every possible pair of regional beta series were computed to generate a {78 × 78} functional connectivity matrix for each participant and each task condition. Fourth, network connectivity and topology were analyzed using graph-based representations of network structure. Network connectivity was analyzed using the values in the correlation matrix. Edge-wise connectivity (SE) reflected the strength of the correlation for each value in the functional connectivity matrix. For example, in the connectivity matrix shown, SE for the connection between region of interest (ROI) 1 and ROI 2 would be .33. Region-wise connectivity (SR) was computed as the sum of each region’s correlation values. For example, SR for ROI 1 is computed as the sum of its correlation values with all other regions. Topologic measures were computed using graph-based representations of network structure as detailed in the main text and Section S.2 in Supplement 1. In the graph-based representation shown, each region is represented as a blue circle plotted according to the stereotactic coordinates of its centroid. Each connection, or edge, is represented as a red line and represents a suprathreshold correlation between regional beta series. The graph has been overlaid on a cortical surface rendering to provide an orientation with respect to approximate anatomical location.

Mean accuracy (left) and reaction time (right) of patients and control subjects in each task condition. Error bars represent standard deviations. *p <.05, corrected.

Brain regions showing significant main effects of cue (top row) and diagnosis (bottom row). Main effects of cue reflected increased functional connectivity in the more difficult B cue condition; main effects of diagnosis reflected reduced functional connectivity in patients compared with control subjects. Effects surviving false-positive correction for multiple comparisons are shown in yellow; those significant at p < .05, uncorrected are shown in red.

Subnetworks of functional connections showing a significant main effect of cue (left column), main effect of diagnosis (middle column) and cue × diagnosis interaction (right column). The top row presents graph-based representations of these subnetworks, with each region represented as a blue circle plotted according to the stereotactic coordinates of its centroid, and each suprathreshold edge represented as a red line. The green edge in the graph for the main effect of cue represents a single edge where connectivity was higher in A cue than B cue trials. For all other edges, connectivity was higher in the B cue condition. For the main effect of diagnosis, all suprathreshold edges reflected reduced connectivity in patients. The graphs are overlaid on cortical surface renderings to provide an orientation with respect to approximate anatomical location. The names of key regions in each subnetwork have been noted for ease of reference. Bottom row presents the proportion of each type of connection in each subnetwork, as categorized according to the lobes each edge interconnects. Amyg, amygdala; Angular, angular gyrus; Fron Inf Oper, inferior frontal operculum; Fron Inf Tri, inferior frontal gyrus, pars Triangularis; Fron Mid, middle frontal gyrus; Fron Sup, superior frontal gyrus; Fron Sup Med, superior frontal gyrus, medial aspect; Hipp, hippocampus; L, left; Ling, lingual gyrus; Mid Cing, midcingulate cortex; Occ Sup, superior occipital gyrus; Par Inf, inferior parietal lobe; Postcentral, postcentral gyrus; Precentral, precentral gyrus; Precun, precuneus; R, right.

Scatterplot of the association between cognitive control reaction time (RT) performance and functional connectivity between right mid-cingulate and superior frontal gyri (R Mid Cing and R Fron Sup in Figure 4) for control subjects (left, blue) and patients (right, red).