Dynamic Changes in ALFF and DC in Subthreshold Depression Before and After ICBT Intervention

Abstract

Purpose: Subthreshold depression (SD) is a highly prevalent mental health condition and a key precursor in major depressive disorder. Internet-based cognitive behavioral therapy (ICBT) effectively treats SD in clinical settings, but the neuromechanisms behind its success are not fully understood. This study aimed to examine changes in intrinsic brain activity in SD and their further alterations after ICBT intervention.

Patients and methods: Twenty-five individuals with SD and 25 matched healthy controls (HC) were enrolled. SD underwent the same MRI scans and clinical assessments before and after a five-week ICBT intervention. HC underwent a single MRI scan during enrollment. The amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) are established analytical techniques in the field of neuroimaging to assess intrinsic brain activity. Two-sample and paired-sample t-tests were employed to examine changes in whole-brain ALFF and DC. Pearson or Spearman correlation analysis was performed to evaluate associations between altered ALFF/DC values and changes in clinical assessment scores in SD.

Results: Compared with HC, decreased DC in the right precuneus (PCUN) and increased ALFF in the right insula (INS) were found in SD before ICBT intervention. After ICBT intervention, ALFF in the left hippocampus (HIP) was increased, and DC in the right medial and paracingulate gyri (DCG) was reduced in SD. Altered ALFF values in the left HIP showed a negative correlation with changes in PHQ-9 scores, and a positive correlation with changes in FATS-ReB scores. Altered DC values in the right DCG were positively correlated with changes in CCTS-TR-BhA scores.

Conclusion: These findings provide new insights into the altered intrinsic brain activities in SD. More importantly, this study found potential changes in intrinsic activity in brain regions associated with ICBT response to SD, which may help further explore the neuropsychological mechanism underlying the efficacy of ICBT in the future.

Keywords: amplitude of low-frequency fluctuation; degree centrality; internet-based cognitive behavioral therapy; resting-state functional magnetic resonance imaging; subthreshold depression.

Figure 1

Study flowchart. Support was provided by Figdraw.

Figure 2

Comparison of ALFF and DC between SD before ICBT intervention and HC. Compared with HC, increased ALFF in the right INS and decreased DC in the right PCUN were found in SD before ICBT intervention (two-tailed voxel-level p < 0.01 and cluster-level p < 0.05, GRF correction).

Figure 3

(A) Comparison of ALFF in SD before and after ICBT intervention. Increased ALFF in the left Hip was found in SD after ICBT intervention (two-tailed voxel-level p < 0.01 and cluster-level p < 0.05, GRF correction). (B) Correlations among the altered ALFF values and clinical measurement scores. Altered ALFF values in the left HIP were negatively correlated with changes in PHQ-9 scores, and positively correlated with changes in FATS-ReB scores.

Figure 4

(A) Comparison of DC in SD before and after ICBT intervention. Decreased DC in the right DCG was found in SD after ICBT intervention (two-tailed voxel-level p < 0.01 and cluster-level p < 0.05, GRF correction). (B) Correlations among the altered DC values and clinical measurement scores. Altered DC values in the right DCG were positively correlated with changes in CCTS-TR-BhA scores.