Neural Correlates and Connectivity Underlying Stress-Related Impulse Control Difficulties in Alcoholism

Dongju Seo, Cheryl M Lacadie, Rajita Sinha, Dongju Seo, Cheryl M Lacadie, Rajita Sinha

Abstract

Background: Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied.

Methods: This study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients, and 37 demographically matched healthy controls were examined during brief individualized imagery trials of stress, alcohol cue, and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale.

Results: Impulse control difficulties in AUD patients were significantly associated with hypo-active response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p < 0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex compared to controls, which are core regions of emotion regulation, suggesting AUD patients' decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p < 0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p < 0.05, with adjusted Bonferroni correction).

Conclusions: Hypo-active response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism.

Keywords: Alcoholism; Caudate; Impulse Control; Prefrontal Cortex; Stress.

Conflict of interest statement

The authors do not have any financial or other interest or relationship that might be perceived to influence the results or interpretation of the manuscript.

Copyright © 2016 by the Research Society on Alcoholism.

Figures

Figure 1
Figure 1
Whole-brain voxel-based correlation results and scatter plots showing negative correlations between impulse control problems and stress induced brain activity in AUD patients. Hypoactive response to stress in the VmPFC (r= −.55), right caudate (r= −.42), and left LPFC (r = −.46) relative to the neutral condition was significantly associated with greater difficulties controlling impulsivity (whole brain FWE corrected at p

Figure 2

Functional connectivity with the VmPFC…

Figure 2

Functional connectivity with the VmPFC seed. When the VmPFC was used as a…

Figure 2
Functional connectivity with the VmPFC seed. When the VmPFC was used as a seed region, significant group difference was found in connectivity between the VmPFC and ACC during stress (p

Figure 3

Functional connectivity with the right…

Figure 3

Functional connectivity with the right caudate seed. When the right caudate was used…

Figure 3
Functional connectivity with the right caudate seed. When the right caudate was used as a seed region, significant group difference was found in connectivity between right caudate and motor cortex during stress (p HC. L= Left, R = Right. MNI coordinates were used.

Figure 4

Functional connectivity with the left…

Figure 4

Functional connectivity with the left lateral PFC seed. When the left LPFC was…

Figure 4
Functional connectivity with the left lateral PFC seed. When the left LPFC was used as a seed region, significant group difference was found in connectivity between the left DLPFC and the DmPFC and sensory motor cortices (including pre-/post- central gyrus, and occipital gyrus) during the stress condition (p HC. DmPFC= Dorsomedial prefrontal cortex; G = Gyrus, L= Left, R = Right. MNI coordinates were used.

Figure 5

Neural connectivity associated with stress-induced…

Figure 5

Neural connectivity associated with stress-induced anxiety in AUD patients. During stress exposure, reduced…

Figure 5
Neural connectivity associated with stress-induced anxiety in AUD patients. During stress exposure, reduced connectivity between the left LPFC and dorsomedial PFC (r= −.44) was associated with greater in-scan, stress-induced anxiety (p <0.05, adjusted Bonferroni correction applied).
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    1. Arnsten AF. Stress signalling pathways that impair prefrontal cortex structure and function. Nature reviews Neuroscience. 2009;10:410–22. - PMC - PubMed
    1. Asplund CL, Todd JJ, Snyder AP, Marois R. A central role for the lateral prefrontal cortex in goal-directed and stimulus-driven attention. Nature neuroscience. 2010;13:507–12. - PMC - PubMed
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Figure 2
Figure 2
Functional connectivity with the VmPFC seed. When the VmPFC was used as a seed region, significant group difference was found in connectivity between the VmPFC and ACC during stress (p

Figure 3

Functional connectivity with the right…

Figure 3

Functional connectivity with the right caudate seed. When the right caudate was used…

Figure 3
Functional connectivity with the right caudate seed. When the right caudate was used as a seed region, significant group difference was found in connectivity between right caudate and motor cortex during stress (p HC. L= Left, R = Right. MNI coordinates were used.

Figure 4

Functional connectivity with the left…

Figure 4

Functional connectivity with the left lateral PFC seed. When the left LPFC was…

Figure 4
Functional connectivity with the left lateral PFC seed. When the left LPFC was used as a seed region, significant group difference was found in connectivity between the left DLPFC and the DmPFC and sensory motor cortices (including pre-/post- central gyrus, and occipital gyrus) during the stress condition (p HC. DmPFC= Dorsomedial prefrontal cortex; G = Gyrus, L= Left, R = Right. MNI coordinates were used.

Figure 5

Neural connectivity associated with stress-induced…

Figure 5

Neural connectivity associated with stress-induced anxiety in AUD patients. During stress exposure, reduced…

Figure 5
Neural connectivity associated with stress-induced anxiety in AUD patients. During stress exposure, reduced connectivity between the left LPFC and dorsomedial PFC (r= −.44) was associated with greater in-scan, stress-induced anxiety (p <0.05, adjusted Bonferroni correction applied).
Figure 3
Figure 3
Functional connectivity with the right caudate seed. When the right caudate was used as a seed region, significant group difference was found in connectivity between right caudate and motor cortex during stress (p HC. L= Left, R = Right. MNI coordinates were used.
Figure 4
Figure 4
Functional connectivity with the left lateral PFC seed. When the left LPFC was used as a seed region, significant group difference was found in connectivity between the left DLPFC and the DmPFC and sensory motor cortices (including pre-/post- central gyrus, and occipital gyrus) during the stress condition (p HC. DmPFC= Dorsomedial prefrontal cortex; G = Gyrus, L= Left, R = Right. MNI coordinates were used.
Figure 5
Figure 5
Neural connectivity associated with stress-induced anxiety in AUD patients. During stress exposure, reduced connectivity between the left LPFC and dorsomedial PFC (r= −.44) was associated with greater in-scan, stress-induced anxiety (p <0.05, adjusted Bonferroni correction applied).

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