Fig. 9: Changes in functional connectivity correlated with changes in general psychopathology and depressive symptoms.

a The change in the peak frequency of global functional connectivity was negatively correlated with the symptom severity in PANSS general psychopathology across all participants and within the tACS treatment group. 8 of 14 participants in the tACS treatment group exhibited a decrease in general psychopathology. Remarkably, 100% of these participants also exhibited an increase in peak frequency of global functional connectivity (red dots in shaded area). Conversely, 9 out of 14 participants in the tACS treatment group exhibited an increase in peak frequency, and 8 of 9 of those participants exhibited a decrease in general psychopathology (with one participant with no change in symptoms). A further breakdown of PANSS general psychopathology subscore showed a significant correlation between peak frequency change and depression (c). b Changes in frontal functional connectivity at the stimulation frequency (10 Hz) were positively correlated with that of PANSS general psychopathology subscore. In other words, a decrease in frontal connectivity improved symptoms. Among the 8 out of 14 participants in the tACS treatment group who exhibited a decrease in symptom severity on Day 5, seven of them also exhibited a decrease in frontal connectivity (shaded area; one participant had virtually no change in frontal connectivity). Note that, in (a) and (b), functional connectivity changes and symptom changes are shown in the original scale for visualization. The statistical results are based on Spearman correlation. Spearman correlation was used for its robustness against outliers (circled). Removing the circled sample points led to qualitatively equivalent results (see text for details).