Cognitive Profiles and Functional Connectivity in First-Episode Schizophrenia Spectrum Disorders - Linking Behavioral and Neuronal Data

Abstract

The character of cognitive deficit in schizophrenia is not clear due to the heterogeneity in research results. In heterogeneous conditions, the cluster solution allows the classification of individuals based on profiles. Our aim was to examine the cognitive profiles of first-episode schizophrenia spectrum disorder (FES) subjects based on cluster analysis, and to correlate these profiles with clinical variables and resting state brain connectivity, as measured with magnetic resonance imaging. A total of 67 FES subjects were assessed with a neuropsychological test battery and on clinical variables. The results of the cognitive domains were cluster analyzed. In addition, functional connectivity was calculated using ROI-to-ROI analysis with four groups: Three groups were defined based on the cluster analysis of cognitive performance and a control group with a normal cognitive performance. The connectivity was compared between the patient clusters and controls. We found different cognitive profiles based on three clusters: Cluster 1: decline in the attention, working memory/flexibility, and verbal memory domains. Cluster 2: decline in the verbal memory domain and above average performance in the attention domain. Cluster 3: generalized and severe deficit in all of the cognitive domains. FES diagnoses were distributed among all of the clusters. Cluster comparisons in neural connectivity also showed differences between the groups. Cluster 1 showed both hyperconnectivity between the cerebellum and precentral gyrus, the salience network (SN) (insula cortex), and fronto-parietal network (FPN) as well as between the PreCG and SN (insula cortex) and hypoconnectivity between the default mode network (DMN) and seeds of SN [insula and supramarginal gyrus (SMG)]; Cluster 2 showed hyperconnectivity between the DMN and cerebellum, SN (insula) and precentral gyrus, and FPN and IFG; Cluster 3 showed hypoconnectivity between the DMN and SN (insula) and SN (SMG) and pallidum. The cluster solution confirms the prevalence of a cognitive decline with different patterns of cognitive performance, and different levels of severity in FES. Moreover, separate behavioral cognitive subsets can be linked to patterns of brain functional connectivity.

Keywords: cluster analysis; cognitive deficit; cognitive profiles; first episodes; heterogeneity; resting state functional connectivity; schizophrenia.

FIGURE 1

Composition of the cognitive domains (Rodriguez et al., 2017).

FIGURE 2

Cognitive performance of the three clusters. Blue line Cluster 1: decline in the VERBM and WM/FLEX domains (z-scores below point -1.0). Red line Cluster 2: decline in the VERBM domain only (z-scores below point -1.0) and above average performance in the ATTV domain (z-scores over point 1.0). Green line: Cluster 3: generalized and severe impairment in all cognitive domains (z-scores ranging from -1.21 in the VISM domain to -3.35 in the WM/FLEX domain). Domains: VISM, visual memory and learning; VERBM, verbal memory and learning; ABSTR/EXEF, abstraction/executive functions; SPOP, speed of processing/psychomotoric speed; ATTV, attention/vigilance; WM/FLEX, working memory/flexibility.

FIGURE 3

Results of multivariate analysis: the main effects of ROIs. The red lines represent positive connections/effects between ROI.

FIGURE 4

Results of the comparison between the cognitive cluster groups and healthy individuals. The red lines represent positive and blue line negative ROI-to-ROI significant effects. The darker red means a higher number of positive than negative effects and the darker blue a higher number of negative than positive effects.