Neurobiological models of impulsivity in borderline personality disorder and healthy individuals

Abstract

Sammendrag (Norwegian summary) Nevrobiologiske modeller for impulsivitet i pasienter med emosjonelt ustabil personlighetsforstyrrelse og friske studiedeltakere I dette doktorgradsarbeidet har jeg testet nevrobiologiske modeller for impulsivitet der pasienter med emosjonelt ustabil personlighetsforstyrrelse (engelsk forkortelse: BPD) og friske deltagere ble gitt impulsivitetstester (go/nogo- og Posner task) under funksjonell hjerneavbildning (fMRI). To typer impulsivitet, drevet av ignoranse for fremtidige hendelser og belønningssensitivitet, er tidligere mye omtalt i litteraturen. Den første typen er betraktet som dysfunksjonell og forbundet med underaktivitet i orbitofrontale korteks. Den andre typen er betraktet som funksjonell og forbundet med dopaminaktivitet i hjernens belønningssentre. Det har vært foreslått at dopaminaktiviteten er sterkere hos belønningssensitive individer med en lav grad av unnvikende personlighetstrekk. Pasienter med BPD er kjent for dikotom tenkning og impulsiv atferd under stress, sannsynligvis relatert til en tredje form for impulsivitet, også denne dysfunksjonell. Min første studie viste at personlighetsskårer på «ignoranse for fremtidige hendelser» både hos friske deltakere og BPD pasienter var forbundet med underaktivitet i orbitofrontale korteks og dysfunksjonell impulsivitet (feiltrykk). Den andre studien på friske deltakere viste at belønningsrelatert hjerneaktivitet i ventrale striatum var sterkest hos ikke-unnvikende, belønningssensitive deltakere og at disse utviste funksjonell impulsivitet (hurtige responser). Den siste studien viste at utfallsusikkerhet – en viktig komponent i stress – ga abnormal aktivitet i høyre insula og anterior cingulate korteks, samt dysfunksjonell impulsivitet (feiltrykk) hos BPD pasienter. Resultatet er fortolket slik at utfallsusikkerhet, kombinert med usikkerhetsintoleranse, induserer dikotome (enten/ eller) forventninger hos BPD pasienter, som et middel for å redusere usikkerheten. Dikotome forventninger leder imidlertid til dysregulert, impulsiv atferd.

My doctoral thesis comprises three fMRI studies which shed light on different neurobiological models of impulsivity and brain systems that regulate behavior in both healthy subjects and patients with borderline personality disorder (BPD). To date, most neurobiological research has been aimed to elucidate two main types of impulsivity. The first type is believed to be driven by reward incentives, implicating dopaminergic brain structures, the ventral striatum in particular. The Joint Subsystems Hypothesis suggests that the level of reward responsivity, and thus its derived impulsivity, is influenced by trait avoidance. The second type is associated with disinhibition, i.e., a tendency to act without much forethought, attributed to prefrontal hypo-activity, particularly in the orbitofrontal cortex. A third type, urgency or distress driven impulsivity, has received less attention and lacks a comprehensive neurobiological model. That type is believed to be relevant for the understanding of impulsivity in BPD patients who are known to exhibit dichotomous thinking and dysregulated impulsive behavior while under distress. The aim of the present research was to elucidate the neuronal correlates of dysfunctional impulsivity in BPD and functional impulsivity in healthy subjects. My coworkers and I enrolled 15 female, unmedicated BPD outpatients and 15 matched, healthy controls (HCs). All subjects filled out two impulsivity self-reports: 1) rash impulsivity items from I7 which measure the tendency to act without much forethought, and 2) reward sensitivity (SR) from the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) which measures incentive drive. In addition, they completed trait avoidance measures, i.e., sensitivity to punishment (SP) from SPSRQ and neuroticism from Eysenck’s Personality Questionnaire. They also subsequently performed a go/nogo- and Posner task during fMRI scanning. The first probes response inhibition of habituated pre-potent responses while the second measures the invigoration of impulsive responses due to cue primes (cue stimuli) which provides partial information of upcoming target stimuli. During the go/nogo-task (Study 1), we demonstrated that I7 rash impulsivity scores across both BPD patients and HCs were associated with a hypoactive orbitofrontal cortex and dysfunctional impulsivity, measured by commission errors. BPD patients made more commission errors than HCs, but no brain activity differences were found between groups. The Posner task in the study of healthy participants (Study 2) revealed that SR predicted functional impulsivity, i.e., enhanced reaction times induced by cue primes and increased activity in the ventral striatum. In addition, those associations were strengthened after adjusting for SP, which is in line with the Joint Subsystems Hypothesis. Based on the Posner task in the last study (Study 3), we showed that BPD patients had more commission errors to incorrectly primed targets, and faster reaction times to correctly primed targets relative to targets preceded by neutral primes, which imply that cue primes induced stronger expectations for the upcoming targets among BPD patients. During the priming phase, the BPD patients showed a larger right mid insular activity decrement and a bilateral anterior cingulate cortex activity increase. The former is interpreted to reflect reduced outcome uncertainty (dichotomous expectations) and the latter an increased inclination to respond. In sum, my research supports the position that impulsivity is underpinned by activity in several brain systems. Reward-driven, functional impulsivity is associated with dopaminergic brain activity, and related to high SR and low SP. A dysfunctional tendency to act without much forethought is related to orbitofrontal hypo-activity. Also, dysfunctional impulsivity induced by outcome uncertainty entails dichotomous expectations for future outcomes and brain activity aberrance in the right mid insula and anterior cingulate cortex in BPD patients. Because outcome uncertainty is an important component in distress, the results may reflect distress (or uncertainty) intolerance in BPD.