The complex nature of physiological systems where multiple organs interact to form a network is complicated by direct and indirect interactions, with varying strength and direction of influence. This study proposes a novel framework which quantifies directional and pairwise couplings, while controlling for the effect of indirect interactions. Simulation results confirm the superiority of this framework in uncovering directional primary links compared to previous published methods. In a practical application of cognitive attention and alertness tasks, the method was used to assess controlled directed interactions between the cardiac, respiratory and brain activities (prefrontal cortex). It revealed increased interactions during the alertness task between brain wave activity on the left side of the brain with heart rate and respiration compared to resting phases. During the attention task, an increased number of right brain wave interactions involving respiration was also observed compared to rest, in addition to left brain wave activity with heart rate. The proposed framework potentially assesses directional interactions in complex network physiology and may detect cognitive dysfunctions associated with altered network physiology.