Predictive utility of task-related functional connectivity vs. voxel activation.

Functional connectivity, both in resting state and task performance, has steadily increased its share of neuroimaging research effort in the last 1.5 decades. In the current study, we investigated the predictive utility regarding behavioral performance and task information for 240 participants, aged 20-77, for both voxel activation and functional connectivity in 12 cognitive tasks, belonging to 4 cognitive reference domains (Episodic Memory, Fluid Reasoning, Perceptual Speed, and Vocabulary). We also added a model only comprising brain-structure information not specifically acquired during performance of a cognitive task. We used a simple brain-behavioral prediction technique based on Principal Component Analysis (PCA) and regression and studied the utility of both modalities in quasi out-of-sample predictions, using split-sample simulations (= 5-fold Monte Carlo cross validation) with 1,000 iterations for which a regression model predicting a cognitive outcome was estimated in a training sample, with a subsequent assessment of prediction success in a non-overlapping test sample. The sample assignments were identical for functional connectivity, voxel activation, and brain structure, enabling apples-to-apples comparisons of predictive utility. All 3 models that were investigated included the demographic covariates age, gender, and years of education. A minimal reference model using simple linear regression with just these 3 covariates was included for comparison as well and was evaluated with the same resampling scheme as described above. Results of the comparison between voxel activation and functional connectivity were mixed and showed some dependency on cognitive outcome; however, mean differences in predictive utility between voxel activation and functional connectivity were rather small in terms of within-modality variability or predictive success. More notably, only in the case of Fluid Reasoning did concurrent functional neuroimaging provided compelling about cognitive performance beyond structural brain imaging or the minimal reference model.