Changes in resting functional connectivity during abstinence in stimulant use disorder: a preliminary comparison of relapsers and abstainers

Abstract

Background: Previously identified resting functional connectivity (FC) differences in individuals with stimulant use disorder (SUD) suggest an imbalance in neural regions that mediate behavioral aspects relevant to addiction such as emotion regulation and reward processing. There is a need to further investigate these differences across time between those that relapse and those that do not. This is the first longitudinal study of recently abstinent SUD (SUD-RA) that identifies specific FC changes in subsequent relapsers (vs abstainers). We hypothesized that (1) subsequent relapsers (vs abstainers) will show lower FC of emotion regulation regions and higher FC of reward processing regions and (2) FC differences would be more evident across time.

Methods: We examined resting FC in 18 SUD-RAs (8 females, age: M=22.05 ± 2.64) and 15 non-substance abusing controls (NSAC; 5 females, age: M=24.21 ± 5.76) at Time 1 (abstinent ∼5 weeks). Fourteen NSAC and 12 SUD-RAs were re-examined at Time 2 (abstinent ∼13 weeks). With seed-based FC measures, we examined FC differences between SUD-RAs that abstained or relapsed over the subsequent 6 months.

Results: Relapsers (vs abstainers) had higher FC between (1) nucleus accumbens (NAcc) and left frontopolar cortex (FPC), (2) NAcc and posterior cingulate gyrus and (3) subgenual anterior cingulate and left FPC at Time 1. Relapsers (vs abstainers) showed larger reduction in FC strength within these regions across time.

Conclusions: Resting FC reduction found in relapsers (vs. abstainers) from 5 to 13 weeks of abstinence may be a biological marker of relapse vulnerability. These preliminary findings require replication with larger sample sizes.

Keywords: Abstinence; Addiction; Change; Frontal; Functional connectivity; Relapse.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

(A) Nucleus accumbens (NAcc) (x=±12, y=10, z=−9) and (B) subgenual anterior cingulate cortex (ACC) (x=5, y=25, z=−10)seeds used to examine strength of functional connectivity overlaid on Montreal Neurological Institute (MNI) brain.

Figure 2

Results showing higher FC between NAcc and FPC at Time 1 but not at Time 2 in REL vs ABS. LEFT: (A) Whole-brain FC maps showing regions with significant connectivity to NAcc (p<0.025, corrected for multiple comparisons) in ABS (1st row) and REL (2nd row). Bottom row shows whole-brain independent samples t-test results in which REL had significantly higher NAcc-FPC than ABS (p<0.025, corrected for multiple comparisons). Functional maps are laid on MNI brains in radiological orientation (right is left). RIGHT: Scatter plots showing z-scores representing strength of NAcc-FPC FC in the NSAC, ABS and REL groups at Time 1 (B) and Time 2 (C). Each dot represents an individual subject’s average z-score within the FPC cluster. Red bar shows significant difference between groups. FC, functional connectivity; NAcc, nucleus accumbens; FPC, frontopolar cortex; REL, stimulant addicts that relapsed over six months; ABS, stimulant addicts that remained abstinent over six months; MNI, Montreal Neurological Institute; NSAC, non-substance abusing controls.

Figure 3

Results showing higher FC between NAcc and PCC at Time 1 but not at Time 2 in REL vs ABS. LEFT: (A) Whole-brain FC maps showing regions with significant connectivity to NAcc (p<0.025, corrected for multiple comparisons) in ABS (1st row) and REL (2nd row). Bottom row shows whole-brain independent samples t-test results in which REL had significantly higher NAcc-PCC than ABS (p<0.025, corrected for multiple comparisons). Functional maps are laid on MNI brains in radiological orientation (right is left). RIGHT: Scatter plots showing z-scores representing strength of NAcc-PCC FC in the NSAC, ABS and REL groups at Time 1 (B) and Time 2 (C). Each dot represents an individual subject’s average z-score within the PCC cluster. Red bars show significant difference between groups. FC, functional connectivity; NAcc, nucleus accumbens; PCC, posterior cingulate cortex; REL, stimulant addicts that relapsed over six months; ABS, stimulant addicts that remained abstinent over six months; MNI, Montreal Neurological Institute; NSAC, non-substance abusing controls.

Figure 4

Results showing higher FC between sgACC and FPC at Time 1 but not at Time 2 in REL when compared to ABS. LEFT: (A) Whole-brain FC maps showing regions with significant connectivity to sgACC (p<0.025, corrected for multiple comparisons) in ABS (1st row) and REL (2nd row). Bottom row shows whole-brain independent samples t-test results in which REL had significantly higher sgACC-FPC than ABS (p<0.025, corrected for multiple comparisons). Functional maps are laid on MNI brains in radiological orientation (right is left). RIGHT: Scatter plots showing z-scores representing strength of sgACC-FPC FC in the NSAC, ABS and REL groups at Time 1 (B) and Time 2 (C). Each dot represents an individual subject’s average z-score within the FPC cluster. Red bars show significant difference between groups. FC, functional connectivity; sgACC, subgenual anterior cingulate; FPC, frontopolar cortex; REL, stimulant addicts that relapsed over six months; ABS, stimulant addicts that remained abstinent over six months; MNI, Montreal Neurological Institute; NSAC, non-substance abusing controls.

Figure 5

Scatter plots showing change in FC between (A) NAcc and FPC, (B) NAcc and PCC and (C) sgACC and FPC. Each dot represents FC change in an individual subject (Time 2 z-score minus Time 1 z-scores). Red bars show significant difference between groups. NAcc, nucleus accumbens; FPC, frontopolar cortex; PCC, posterior cingulate cortex; sgACC, subgenual anterior cingulate; REL, stimulant addicts that relapsed over six months; ABS, stimulant addicts that remained abstinent over six months; FC, functional connectivity.