Background Pain is often a complaint that precedes total knee arthroplasty (TKA), however the procedure itself is associated with considerable post-operative pain lasting days to weeks which can predict longer-term surgical outcomes. Previously, we reported significant opioid-sparing effects of motor cortex transcranial direct current stimulation from a single-blind trial. In the present study, we used double-blind methodology to compare motor cortex tDCS and prefrontal cortex tDCS to both sham and active-control (active electrodes over non-pain modulating brain areas) tDCS. Methods 58 patients undergoing unilateral TKA were randomly assigned to receive 4 20-minute sessions (a total of 80 minutes) of tDCS (2mA) post-surgery with electrodes placed to create 4 groups: 1) MOTOR (n=14); anode-motor/cathode-right prefrontal, 2) PREFRONTAL (n=16); anode-left-prefrontal/cathode-right-sensory, 3) ACTIVE-CONTROL (n=15); anode-left-temporal-occipital junction/cathode-medial-anterior-premotor-area, and 4) SHAM (n=13); 0mA-current stimulation using placements 1 or 2. Patient controlled analgesia (PCA; hydromorphone) use was tracked during the ∼72-hours post-surgery. Results Patients in the sham group and the active-control group used 15.4mg (SD=14.1) and 16.0mg (SD=9.7) of PCA hydromorphone respectively. There was no difference between the slopes of the cumulative PCA usage curves between these two groups (p=.25; ns). Patients in the prefrontal tDCS group used an average of 11.7mg (SD=5.0) of PCA hydromporhone, and the slope of the cumulative PCA usage curve was significantly lower than sham (p<.0001). However, patients in the motor tDCS group used an average of 19.6mg (SD=11.9) hydromorphone and the slope of the PCA use curve was significantly higher than sham (p<.0001). Conclusions Results from this double-blind cortical-target-optimization study suggest that anodal transcranial direct current stimulation (tDCS) over the left prefrontal cortex may be a reasonable approach to reducing post-TKA opioid requirements. Given the unexpected finding that motor cortex failed to produce an opioid sparing effect in this follow-up trial, further research in the area of post-operative cortical stimulation is still needed.

The aim of this study was to investigate the topological reorganization of the brain default mode network (DMN) in patients with irritable bowel syndrome (IBS) using resting-state functional magnetic resonance imaging (rs-fMRI). With approval by our ethics committee, rs-fMRI was prospectively performed in 31 IBS patients (25 male, 27 ± 8 years) and 32 healthy controls (25 male, 29 ± 9 years). The DMN was determined by unbiased seed-based functional connectivity (FC) analysis and then parcellated into several subregions. FC across all pairs of DMN subregions was computed to construct the DMN architecture, for which topological properties were characterized by graph theoretical approaches. Pearson correlation was performed between abnormal DMN inter-regional FC and network measures and clinical indices in IBS patients. Compared to healthy controls, IBS patients showed decreased DMN inter-regional FC between the anterior cingulate cortex and precuneus, the medial orbital of the superior frontal gyrus (ORBsupmed) and precuneus, and the middle temporal gyrus and precuneus. IBS patients also showed decreased DMN global efficiency (E ). Inclusion of anxiety and depression as covariates abolished FC between ORBsupmed and precuneus and some E differences. The average DMN FC was positively correlated with average E (r = 0.47, P = 0.008) and negatively correlated with symptom severity score (r = -0.37, P = 0.04) in IBS patients. In conclusion, IBS patients showed topological reorganization of the DMN to a non-optimized regularity configuration, which may partly be ascribed to high levels of anxiety and depression.

Functional connectivity changes in the DMN, which were associated with improved hematocrit levels and cognitive function, may recover earlier than structural connectivity changes do 1 month after renal transplantation.

• 70 kVp cerebral CTA is feasible and provides diagnostic image quality. • 70 kVp cerebral CTA resulted in 85% effective dose reduction. • S4 level of SAFIRE is recommended for 70 kVp cerebral CTA.

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