The Impact of Perceived Stress on Cortical GABA and Resting State Functional Connectivity

Jessica Busler, PhD, MPS

Brigham and Women’s Hospital
The Impact of Perceived Stress on Cortical GABA and Resting State Functional Connectivity

Scientific Abstract

 

Background: Stress exposures and dysregulated psychological and physiological responses to stress are implicated in psychiatric disorders including disorders of mood, anxiety and cognition. Stress impacts functioning in limbic system brain regions and prefrontal cognitive control regions. Alterations in GABAergic function, the primary inhibitory neurotransmitter in the brain, may underlie stress-induced functional changes in these regions, however, this has not yet been explored within the context of perceived stress. The goal of the current study was to examine associations between perceived stress, GABA levels in prefrontal cognitive control regions, and alterations in resting state functional connectivity.

Methods: 12 women and 6 men, ages 35-61, participated in this study. MR spectroscopy, using STEAM localization at 7 Tesla, was used to measure cortical GABA levels in the brain in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and ventromedial prefrontal cortex (VMPFC). Resting state scans were acquired at 3 Tesla and used to measure functional connectivity (FC) between the default mode network (DMN), salience network (SN), central executive network (CEN), hippocampus, and amygdala. We tested relationships between measures of perceived stress (Perceived Stress Score [PSS]), regional GABA, and FC.

Results: We observed a significant negative correlation between PSS and DLPFC GABA levels (r=-0.62, p=0.023). PSS was also significantly related to left lateral prefrontal cortex (LPFC)- right amygdala FC (r=-0.57, p=0.043). However, we did not observe a significant correlation of DLPFC GABA levels with left LPFC-right amygdala FC (r=0.25, p=0.380).

Conclusions: These preliminary results support a role for perceived stress in dysregulated GABAergic functioning in a core node of the CEN, an intrinsic network thought to underlie goal- directed attentional processes. Our findings also extend previous work suggesting that CEN FC is disrupted by perceived stress and may contribute to the development of novel treatment strategies to improve outcomes in stress-related conditions.

Model Summaryb

 

Model

 

R

 

R Square

Adjusted R Square

Std. Error of the Estimate

1

.646a

.418

.301

.4942633130

00000

  1. Predictors: (Constant), Perceived Stress FF, Age
  2. Dependent Variable: DLPFC_GABA

ANOVAa

 

Model

 

Sum of Squares

 

df

Mean Square

 

F

 

Sig.

1

Regression

1.752

2

.876

3.586

.067b

Residual

2.443

10

.244

 

 

Total

4.195

12

 

 

 

  1. Dependent Variable: DLPFC_GABA

 

  1. Predictors: (Constant), Perceived Stress FF, Age

Coefficientsa

Unstandardized Coefficients

Standardized Coefficients

 

 

t

 

 

Sig.

Model

 

B

Std. Error

Beta

1

(Constant)

5.459

1.711

 

3.191

.010

Age

-.024

.023

-.328

-1.028

.328

Perceived Stress FF

-.048

.019

-.811

-2.543

.029

  1. Dependent Variable: DLPFC_GABA

SoundCloud Transcript

Increased perceived stress, stress exposures, and dysregulated responses to stress are implicated in psychiatric disorders including disorders of mood anxiety and cognition. Stress impacts functioning in limbic and prefrontal control brain regions such as the anterior cingulate, ventromedial prefrontal cortex, and the dorsolateral prefrontal cortex. Alterations and GABAergic function, the primary inhibitory neurotransmitter in the brain, may underlie stress induced functional changes in these regions. In the current study we examined the association of perceived stress with GABA levels in prefrontal cortical control regions, along with corresponding alterations in resting state functional connectivity. In this preliminary study we had 12 women and 7 men that participated. We used MR spectroscopy at 7 Tesla to assess GABA levels in the ACC, VMPFC, and the DLPFC. We also acquired resting state data at 3 Tesla that was used for resting state functional connectivity analyses. We assessed associations between perceived stress and GABA levels as well as perceived stress and GABA levels with resting state functional connectivity. We observed that perceived stress scores were negatively correlated with DLPFC GABA levels. We further saw that functional connectivity from the left lateral prefrontal cortex to the right amygdala was significantly related to perceived stress scores. We did not observe any other significant relationships between perceived stress scores and GABA levels in the ventromedial prefrontal cortex or the ACC. Nor did we observe any other significant relationships of perceived stress scores with other resting state functional connectivity measures. These preliminary results support an association between perceived stress and dysregulated GABAergic functioning in a core node of the central executive network an intrinsic network thought to underlie goal directed attentional processes. In future directions, we hope to examine GABA as a potential modifier of the relationship between perceived stress and resting state functional connectivity as well as the impact of diagnosis and age in a larger sample.

Live Zoom Session – April 21st

research Areas

Authors

Jessica N. Busler, MPS, PhD, Eduardo Coello, PhD, Vicky Liao, BS, Alexander P. Lin, PhD, Laura M. Holsen, PhD, Pamela B. Mahon, PhD