Altered functioning of the executive control circuit in late-life depression: episodic and persistent phenomena

Abstract

Objective: To characterize the functional neuroanatomy of late-life depression (LLD) by probing for both episodic and persistent alterations in the executive-control circuit of elderly adults.

Design: Event-related functional magnetic resonance imaging (fMRI) data were collected while participants performed an executive-control task.

Setting: Participants were recruited through a depression-treatment study within the Pittsburgh, PA, Intervention Research Center for Late-Life Mood Disorders.

Participants: Thirteen nondepressed elderly comparison participants and 13 LLD patients.

Intervention: The depressed patients underwent imaging before initiating and after completing 12 weeks of paroxetine.

Measurements: Regional fMRI activity was assessed in the dorsolateral prefrontal cortex (dLPFC: BA9 and BA46 bilaterally) and the dorsal anterior cingulate cortex (dACC). Functional connectivity was assessed by correlating the fMRI time-series in the dLPFC and dACC.

Results: Both depressed and comparison participants performed the task as expected, with greater response latency during high versus low-load trials. The response-latency load-effect did not differ between groups. In contrast to the null findings for behavioral data, pretreatment, depressed patients showed diminished activity in the dLPFC (BA46 left, t(25)=1.9, p = 0.035) and diminished functional connectivity between the dLPFC and dACC. Moreover, right dLPFC (BA46 right, t(25)=2.17, p < 0.02) showed increased activity after treatment.

Conclusions: These results support a model of both episodic and persistent neurobiologic components of LLD. The altered functional connectivity,perhaps due to vascular damage to frontal white matter, appears to be persistent. Further, at least some of the prefrontal hypoactivity (in the right dLPFC) seems to be an episodic characteristic of acute depression amenable to treatment.

Figure 1

Individual trial of the POP task. Red or Green square is followed, after a 10-second delay, by an arrow pointing to the right or the left.

Figure 2

Behavioral results during the fMRI scanning, reaction time (a) and accuracy (b). Error bars represent +/- 1 standard deviation of the mean.

Figure 3

Time-series for fMRI activation in the dLPFC (BA46). The regions of interest (a) are displayed on the reference□brain, and percent signal change over the course of a trial are shown □for both right BA46 (b) and left BA46 (c).□□

Figure 4

Mean percent signal change on high-load and low-load trials shown for the 5 ROIs. Error bars represent +/- 1 standard deviation of the mean.

Figure 5

Mean normalized correlation coefficients of time series in Elderly Comparison Participants (EC), LLD pre-treatment (Pre-Rx), and LLD post-treatment (Post-Rx) between dACC and BA46 right. Correlations were performed on the extracted fMRI time-series, comparing the peak at dACC during the decision phase of a trial with the peak in left BA46 during the cue phase of the next trial, thus estimating the trial-to-trial PFC adjustment based on ACC conflict. Error bars represent +/- 1 standard deviation of the mean.

Figure 6

Mean normalized correlation coefficients of timeseries in Elderly Comparison Participants (EC), LLD pre-treatment (Pre-Rx), and LLD post-treatment (Post-Rx) between dACC and BA46 right. Correlations were performed on the extracted fMRI time-series, comparing the peak at dACC during the decision phase of a trial with the peak in left BA46 during the cue phase of the next trial, thus estimating the trial-to-trial PFC adjustment based on ACC conflict. Error bars represent +/- 1 standard deviation of the mean.