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Neurobiological models of impulsivity in borderline personality disorder and healthy individuals

Mortensen, Jørgen Assar
Doctoral thesis
Åpne
Fulltext not avialable (Låst)
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http://hdl.handle.net/11250/2450629
Utgivelsesdato
2017
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  • Institutt for nevromedisin og bevegelsesvitenskap [1713]
Sammendrag
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.
 
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Doctoral theses at NTNU;2017:51

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