Fig. 5: Differences between directed connectivity across hemispheres correlate with MDD symptom severity.

The ‘hemispheric differential’ (x-axis) refers to the subtractive difference between directed connectivity in the right-minus-left hemisphere. Therefore, positive values on the x-axis indicate the strength of right hemisphere bias, and negative values indicate the strength of left hemisphere bias. In order to quantify their relationship to depression, the hemispheric differential scores were subjected to the same GEE analysis structure depicted in Fig. 3. A Symptom severity was higher when \({{OFC}}_{{right}}\to {{dlPFC}}_{{right}}\) was greater than \({{OFC}}_{{left}}\to {{dlPFC}}_{{left}}\), which indicates a right hemispheric bias (p < 0.001). B Directed connectivity between the OFC and ACC showed a left hemispheric bias, where symptom severity decreased when \({{OFC}}_{{left}}\to {{ACC}}_{{left}}\) was higher than \({{OFC}}_{{right}}\to {{ACC}}_{{right}}\) (p < 0.001). C Communication between the left dlPFC and ACC was also biased towards the left hemisphere (p = 0.039). Symptom severity increased when \({{dlPFC}}_{{left}}\to {{ACC}}_{{left}}\) was greater than \({{dlPFC}}_{{right}}\to {{ACC}}_{{right}}\). These results provide clear evidence that the right PFC and left PFC play separate roles in major depression. All results were false-discovery rate (FDR) corrected for multiple comparisons across hemispheres. Dotted lines indicate 95% confidence bounds. OFC orbitofrontal cortex, dlPFC dorsolateral prefrontal cortex, ACC anterior cingulate cortex.