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.