Pre- and post-task resting-state differs in clinical populations

Abstract

Resting-state functional connectivity has generated great hopes as a potential brain biomarker for improving prevention, diagnosis, and treatment in psychiatry. This neuroimaging protocol can routinely be performed by patients and does not depend on the specificities of a task. Thus, it seems ideal for big data approaches that require aggregating data across multiple studies and sites. However, technical variability, diverging data analysis approaches, and differences in data acquisition protocols introduce heterogeneity to the aggregated data. Besides these technical aspects, a prior task that changes the psychological state of participants might also contribute to heterogeneity. In healthy participants, studies have shown that behavioral tasks can influence resting-state measures, but such effects have not yet been reported in clinical populations. Here, we fill this knowledge gap by comparing resting-state functional connectivity before and after clinically relevant tasks in two clinical conditions, namely substance use disorders and phobias. The tasks consisted of viewing craving-inducing and spider anxiety provoking pictures that are frequently used in cue-reactivity studies and exposure therapy. We found distinct pre- vs post-task resting-state connectivity differences in each group, as well as decreased thalamo-cortical and increased intra-thalamic connectivity which might be associated with decreased vigilance in both groups. Our results confirm that resting-state measures can be strongly influenced by prior emotion-inducing tasks that need to be taken into account when pooling resting-state scans for clinical biomarker detection. This demands that resting-state datasets should include a complete description of the experimental design, especially when a task preceded data collection.

Keywords: Clinical biomarkers; Functional connectivity; Nicotine addiction; Pre-post changes; Resting-state; Specific phobia.

Graphical abstract

Fig. 1

Brain regions used as seeds in seed-based analyses and ROI-to-ROI analyses. Masks for the bilateral amygdala, dorsal striatum (putamen and caudate), ventral striatum/nucleus accumbens, thalamus, insula, hippocampus and anterior cingulate cortex (ACC) were taken from the Harvard-Oxford atlas. A mask for the medial prefrontal cortex (mPFC) was derived from the Brain Connectome Project dataset and provided by the CONN toolbox.

Fig. 2

ROI-to-ROI pre-post functional connectivity matrix and bar plots. The upper part of the matrix contains rsFC before the task, and post-task rsFC is mirrored on the lower half. (A) In the nicotine use disorder dataset, paired-t-tests (°p-unc < 0.05, two-tailed) comparing pre and post task rsFC showed a decrease in nucleus accumbens–mPFC, thalamus-amygdala, thalamus-insula, and an increase in hippocampus-amygdala and insula-hippocampus, but none survived Bonferroni correction. (B) In the spider phobia dataset, mPFC-amygdala, mPFC-hippocampus, thalamus-amygdala, and thalamus-hippocampus rsFC significantly decreased, with the last two connections being significant after Bonferroni correction (*p < 0.05/28 = 0.0018). Abbreviations: medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC). Error bars in bar plots correspond to SEM. Nsmokers = 29. Nphobia = 37.

Fig. 3

Seed-based functional connectivity changes following a smoking cue-reactivity task and a phobic cue-reactivity task in nicotine use disorder and spider phobia, respectively. Voxel-level p < 0.001 and cluster-level p-FDR < 0.05 without correction for multiple seeds were used here as significance threshold for illustrative purposes. Clusters that survived an additional Bonferroni correction for multiple seed testing are reported in Table 1, Table 2.

Fig. 4

Thalamus seed-based functional connectivity pre-post changes in nicotine use disorder and spider phobia. Intra-thalamic connectivity increased, and cortico-thalamic connectivity decreased in both groups after a visual task. Voxel-level p < 0.001 and cluster-level p-FDR < 0.05.