Neural Substrates of Emotion in Borderline Patients

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DESCRIPTION (provided by applicant): Borderline personality disorder (BPD) is a persistent and severe mental disorder with high mortality, morbidity and levels of distress. Emotional dysregulation or reactivity to environmental events, particularly events such as separations, frustrations, or losses is considered a defining feature of this disorder. This disorder, has received little investigative scrutiny and the neural correlates of abnormal emotional processing are not understood. Startle eyeblink modification (SEM) methodology provides a non-verbal, quantitative tool for the study of emotional processing. When a brief startle stimulus is presented during an unpleasant stimulus, the amplitude of the startle response is potentiated; a pleasant stimulus occasions a relative inhibition of the startle response; and a neutral stimulus is intermediate. This study uses SEM and functional neuroimaging (event-related fMRI and FDG-PET) to explore the intensity, time course, habituation and functional neuroanatomy of emotional responses in three rigorously screened groups: 26 BPD patients (with no comorbid Axis I disorder or Cluster A or C personality disorders), 26 non-BPD patients (with a diagnosis of schizotypal personality disorder and no comorbid Cluster B or C personality disorders or Axis I disorder) and 26 healthy controls. During both the fMRI scan and FDG-uptake for PET, participants will view an intermixed series of unpleasant (e.g., hate), pleasant (e.g., happy) and neutral (e.g., view) words. SEM amplitude difference scores (e.g., unpleasant-pleasant) measured during simultaneous FDG uptake will provide a measure of the intensity, time course, and habituation of emotional processing of unpleasant stimuli and be correlated with regional glucose metabolism. fMRI BOLD response difference scores in key brain regions will provide measurement of the intensity and time course of brain activation. We focus on three brain regions thought to be involved in emotional processing: amygdala, anterior cingulate, and prefrontal cortex (orbitofrontal and dorsolateral). These regions are part of a brain circuit thought to mediate emotional experience and play a significant role in the expression of BPD symptoms. This proposed combination of a psychophysiological and functional neuroanatomy approach holds the potential to provide much-needed information on normative aspects of emotional processing and insights into the neuroanatomy underlying the emotional dysregulation observed in BPD.