ACC GABA levels predict activity and connectivity in the fronto-striatal network during interference inhibition in borderline personality disorder
Guoying Wang1, Julia van Eijk1, Traute Demirakca1, Markus Sack1, Sylvia Cackowski2, Annegret Krause-Utz2, Christian Schmahl2, and Gabriele Ende 1

1Neuroimaging, Central Institute of Mental Health, Mannheim, Germany, 2Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany

Synopsis

By combining the MRS and fMRI technique, we tested whether ACC GABA levels would predict the activity and connectivity in fronto-striatal networks during interference inhibition (Simon task) in BPD patients. BPD patients showed a significant positive correlation between ACC GABA levels and BOLD responses in fronto-striatal regions during interference inhibition. Additionally, ACC GABA levels in BPD patients were positively related to ACC-caudate functional connectivity during the incongruent condition. Our findings highlight that the GABAergic system in the ACC plays an important role in the modulation of impulsivity via regulating the local neural activity and remote connectivity between key regions.

Background

Impulsivity is a clinical hallmark of borderline personality disorder (BPD).1 Motor response inhibition and interference control are aspects of behavioral impulse control, often used to assess impulsivity. 2 As a key region in fronto-striatal circuits, the anterior cingulate cortex (ACC) is crucial for conflict monitoring and rich in γ-Aminobutyric acid (GABA) innervation, but also important for BPD pathology. 3, 4 In this study, we tested whether ACC GABA levels would predict the activity and connectivity in the fronto-striatal network during interference inhibition in BPD patients.

Methods

26 female BPD patients (26.77±6.55 years) and age-matched 25 female healthy controls (HCs) (27.53±6.59 years) were included. In vivo single voxel 1H-MRS using a MEGA-PRESS editing sequence was applied to acquire GABA data in the bilateral ACC voxel (40x30x20mm3) during the resting state (Fig.1). Afterwards, a Simon task was presented by an event-related design consisting of incongruent trails and congruent trials, in order to evaluate the interference inhibition. All images were acquired in a 3T scanner (MAGNETOM TimTrio; Siemens, Erlangen, Germany). GABA spectra were quantified with the jMRUI software. The fMRI data was carried out using statistical parametric mapping (SPM8). The generalized psycophysiogical interaction (gPPI) was performed for the task-modulated functional connectivity analysis, and bilateral ACC were chosen as a seed ROI based on the automated atlas labeling (AAL) parcellation. To examine the associations between ACC GABA levels and task-related BOLD response as well as, connectivity with ACC, a series of whole-brain voxel wise regression analysis were performed via SPM for both individual groups. The ACC GABA levels for each participant served as the regressor of interest for all analyses. The significance levels were set to P < 0.001(uncorrected) on a cluster level of ≥ 10 voxels.

Results

No group difference between BPD patients and HCs was observed at the behavioral level. Compared to HCs, BPD patients showed no difference in BOLD response but lower ACC-caudate connectivity in response to incongruent vs. congruent trials (Fig. 2(a)). This altered connectivity effect was driven by the decrease in ACC-caudate connectivity during the incongruent condition (Fig. 2(b)), and no group difference in connectivity with bilateral ACC was observed during the congruent condition. ACC GABA levels in BPD patients did not differ from HCs. BPD patients showed a significant positive correlation of the GABA levels and the BOLD response in fronto-striatal regions (including ACC, putamen, frontal areas and caudate) when reacting to incongruent vs. congruent trials (Fig. 3). Additionally, GABA levels in the ACC in BPD patients were positively related to ACC-caudate functional connectivity during the incongruent condition (Fig. 4). Those significant correlation effects were not found in the HCs group.

Conclusions

Our results suggested disturbed ACC–caudate functional integration in BPD patients although they performed similarly compared to healthy subjects during interference inhibition in an emotionally neutral state. Moreover, this is the first evidence of a modulatory effect of ACC GABA levels on task-related recruitment and integration of fronto-striatal networks during interference inhibition in BPD patients. Our finding highlights that the GABAergic system in the ACC might play an important role in the modulation of impulsivity via regulating the local neural activity and remote connectivity between key regions.

Acknowledgements

No acknowledgement found.

References

1. Sebastian A, Jung P, Krause-Utz A, Lieb K, Schmahl C, Tuscher O. Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder. Front Hum Neurosci. 2014;8:698.

2. Stahl C, Voss A, Schmitz F, Nuszbaum M, Tuscher O, Lieb K, Klauer KC. Behavioral components of impulsivity. J Exp Psychol Gen. 2014;143(2):850-886.

3. Ende G, Cackowski S, Van Eijk J, Sack M, Demirakca T, Kleindienst N, Bohus M, Sobanski E, Krause-Utz A, Schmahl C. Impulsivity and Aggression in Female BPD and ADHD Patients: Association with ACC Glutamate and GABA Concentrations. LID - 10.1038/npp.2015.153 [doi]. 2015(1740-634X (Electronic)).

4. Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res. 2002;53(2):647-654.

Figures

The MRS voxel.

Brain regions show lower task-modulated brain connectivity with bilateral ACC in BPD patients compared to healthy controls in response to (a) incongruent trials vs. congruent trials (b) incongruent trials. The bar-graph represents the gPPI strength for the significant cluster.

Associations between ACC GABA levels and brain activation during incongruent trials vs. congruent trials in BPD patients. The scatter plot represents the correlation effects for the significant cluster.

Associations between ACC GABA levels and ACC-caudate connectivity during the incongruent condition in (a) the combined group and (b) BPD patients. The scatter plot represents the correlation effects for the significant cluster.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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