ArticleFrontiers in psychiatry2026
Multi-voxel MR-spectroscopy signatures and associations with EEG network hyperexcitability and clinical symptomatology in borderline personality disorder.
Article in Frontiers in psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Previous studies have reported altered gamma-aminobutyric acid (GABA) and glutamate levels in borderline personality disorder (BPD), suggesting disruptions in excitatory-inhibitory neurotransmission. Electroencephalographic (EEG) research has indicated potential network hyperexcitability in BPD, evidenced by increased intermittent rhythmic delta and theta activity (IRDA/IRTA), which may reflect compensatory stabilization mechanisms. This study used multi-voxel magnetic resonance spectroscopic imaging (MRSI) to explore neurochemical abnormalities and their relationships with IRDA/IRTA, psychometric and neuropsychological measures. Methods: Sixty-six female patients diagnosed with BPD (mean age: 30.2 ± 9.7 years) and 29 age-matched female healthy controls (mean age: 27.8 ± 8.0 years) received spirally encoded 3D MRSI scans. GABA, glutamate plus glutamine (Glx), total creatine (tCr) and total N-acetylaspartate (tNAA) were quantified and reported as ratios relative to tNAA and/or tCr. The resulting spectroscopic images were analyzed using LCModel and FreeSurfer software, and IRDA/IRTA detection in a clinical EEG session was performed using independent component analysis. Metabolite ratios were analyzed using hierarchical linear mixed-effects models (ROIs nested within participants), with fixed effects of group or, in separate models, continuous predictors (IRDA/IRTA and psychometric/neuropsychological measures), ROI, and their interaction, and a subject-level random intercept. ROI-specific effects were quantified using estimated marginal means and within-ROI contrasts (emmeans). Results: No metabolite ratio showed a significant BPD vs. control difference. In BPD, IRDA/IRTA-related measures were positively associated with Glx/tCr and Glx/tNAA in the accumbens, and with Glx/tCr in the right caudal anterior cingulate cortex (cACC). BSL-supplement scores showed ROI-dependent associations with tCr/tNAA, with positive ROI-specific effects in the bilateral caudate, right pallidum, and right putamen. Alertness measures were linked to GABA/tCr, Glx/tNAA, and tCr/tNAA (including caudate, pallidum/putamen, cACC, and thalamus), while divided attention omissions and working-memory errors were associated with higher Glx/tCr in the cACC, isthmus cingulate, and hippocampus. ROI-dependent associations were also observed for IQ and verbal learning/recognition with GABA/tCr and tNAA/tCr. Discussion: While no robust group differences emerged, mixed-models using continuous predictors linked higher Glx ratios in nucleus accumbens/cACC to IRDA/IRTA and higher striatal tCr/tNAA to BPD symptom severity and neurocognitive performance. These exploratory multimodal signatures point to cortico-striato-limbic mechanisms in BPD and should be confirmed in larger samples.
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