Background: Borderline personality disorder (BPD) is characterized by deficits in self-regulation, including impulsivity and affective instability. Transference-focused psychotherapy (TFP) is an evidence-based treatment with proven effectiveness in reducing symptoms across multiple cognitive-emotional domains in patients with BPD. In this study, longitudinal changes in neural activation patterns and predictors of treatment response were investigated using a dimensional symptom-based approach. Methods: A functional magnetic resonance imaging (fMRI) activation paradigm was used pre and post-TFP in patients with BPD, with statistical parametric analyses, to test hypotheses concerning the identification of frontolimbic biomarkers for clinical improvement. Using a within-subjects design, BPD subjects (N=10; mean age=27.8) were scanned pretreatment, and again after approximately one-year of TFP using a disorder-specific emotional linguistic go/no-go fMRI paradigm. Results: Analyses confirmed significant treatment related effects with relative increases in dorsal prefrontal cognitive control regions (dorsal anterior cingulate cortex, dorsolateral prefrontal cortex), and relative decreases in ventrolateral prefrontal and hippocampal areas following treatment. Clinical improvement in affective lability correlated positively with activity in left posterior-medial orbitofrontal cortex/ventral striatum (small-volume-corrected p value (psvc)=0.028); right amygdala/ parahippocampal activation correlated negatively with improvements in affective lability (psvc=0.005). Pretreatment hypoactivation in the left posterior-medial orbitofrontal cortex/ventral striatum predicted improvements in affective lability (psvc=0.013), and posttreatment improvements in constraint were predicted by pretreatment right anterior-dorsal anterior cingulate cortex hypoactivation (psvc=0.002). Conclusions: Individuals with BPD whose symptoms improved following TFP demonstrated modulation of neural activity in brain regions known to be implicated in behavioral inhibition in the context of negative emotional processing.