Executive functions after focal lesions to the lateral, orbital and medial subdivisions of the prefrontal cortex : neuropsychological, behavioral and electrophysiological findings
Appears in the following Collection
- Psykologisk institutt 
AbstractExecutive functions (EF) ensure goal-directed behavior and flexible adaptation to changing environmental requirements. EF enable us to plan and anticipate future events, with the capacity to control and distribute attentional resources being an important part of normal EF. Executive deficit is common following acquired brain injury and results in problems with higher-order control over thoughts, emotions and behavior. Presence of executive problems complicates the rehabilitation process and has negative impact on long-term outcome.
Executive control is mediated by distributed but anatomically dissociable neural networks where the prefrontal cortex (PFC) plays an important role. Three main frontal-subcortical circuits involving the lateral (LPFC), orbital (OFC), and medial (MPFC) subdivisions of PFC have been suggested. Each neurocircuitry is thought to subserve partly different functions. Whereas LPFC is primarily associated with cognitive aspects of EF, OFC is related to emotional self-regulation. The MPFC is involved in motivation and energization, and is suggested to play a role in detection and monitoring of cognitive conflict.
Debate persists with regard to the level of regional specificity and functional fractionation within PFC. It has been argued that EF is subserved by distinct and dissociable functions with specific anatomical substrates, but also that the key feature distinguishing the PFC is the high level of flexibility and adaptability across sensory modalities and cognitive domains. Progress in revealing the neural underpinnings of EF requires a high level of conceptual and anatomical specificity. It has been suggested that future developments will be dependent upon research that combines knowledge and methodological approaches from clinical neuropsychology, neurology, cognitive neuroscience and modern imaging techniques.
A main aim of the current study was to examine distinct cognitive control functions associated with the three main subdivisions of the PFC. To this end, a neurocognitive, electrophysiological and lesion study approach was adopted. Patients with focal lesions to one of the three subdivisions of PFC were included and assessed with neuropsychological behavioral tests as well as a questionnaire measure of executive functions in every-day living. Electrophysiological indices of attentional control following focal PFC lesions were also studied with event-related potentials (ERPs) in two experimental tasks. An auditory Novelty Oddball task allowed investigation of novelty and target processing, while a Stop-Signal Task (SST) provided information about motor inhibition and error-monitoring.
In Paper I, novelty and target processing was compared in patients with OFC and LPFC lesions and healthy controls. In paper II, neurocognitive functioning and self- and informant reported executive problems in everyday living were explored in patients with OFC and LPFC lesions. In paper III, the effect of unilateral MPFC damage including the anterior cingulate cortex (ACC) was investigated in two patients who were assessed with neuropsychological and questionnaire measures as well as ERPs in the Novelty Oddball and SST tasks.
The findings reported in paper II largely confirmed our hypothesis that LPFC damage is particularly prone to cause cognitive executive deficit with reductions on tasks demanding sustained mental effort, working memory, response inhibition, and mental switching, while OFC injury is more strongly associated with self-reported dysexecutive symptoms in everyday living. The findings confirmed a functional dissociation between LPFC and OFC.
Paper I and III on the other hand, showed that lesions to all three subdivisions of PFC resulted in altered processing of unexpected novel events, indexed by attenuation of the frontal Novelty P3 response. The findings extend current knowledge in suggesting that not only LPFC, as shown in previous studies, but OFC as swell as MPFC play a role in novelty processing. The studies therefore confirm a role of PFC in novelty processing, but do not lend strong support for a high degree of regional specificity within PFC. Target detection seems not to be critically dependent upon the PFC, as the target-related parietal P3b was normal after lesions to both OFC, LPFC and MPFC.
The results in paper III did not confirm suggestions that the ACC is not involved in cognitive control, as the two patients displayed learning and memory deficit as well as an abolished Novelty P3. Interestingly, the error-related negativity (ERN) was however present in both patients, indicating that error detection can occur despite unilateral ACC lesion. In summary, the findings from the three studies lend support both to theories that highlight functional and anatomical specificity of distinct control functions within the PFC, as well as theories that emphasize adaptive, supramodal properties of the frontal lobes in complex tasks.
List of papers. Papers II and III are removed from the thesis due to copyright restrictions.
Paper I: Løvstad, M., Funderud, I., Lindgren, M., Endestad, T., Due-Tønnessen, P., Meling, T.R., Voytek, B., Knight, R.T., & Solbakk, A.K. (2012). Contribution of subregions of human frontal cortex to novelty processing. Journal of Cognitive Neuroscience, 24(2), 378-395. doi:10.1162/jocn_a_00099 Copyright 2011 Massachusetts Institute of Technology
Paper II: Løvstad, M., Funderud, I., Endestad, T., Due-Tønnessen, P., Meling, T.R., Lindgren, M., Knight, R.T., & Solbakk, A.K. (2012). Executive functions after orbital or lateral prefrontal lesions: Neuropsychological profiles and self-reported executive functions in everyday living. Brain Injury. 26(13-14), 1586-98. doi:10.3109/02699052.2012.698787
Paper III: Løvstad, M., Funderud, I., Meling, T., Krämer, U.M., Voytek B., Due-Tønnessen, P., Endestad, T, Lindgren, M., Knight, R.T., & Solbakk, A.K (2012). Anterior cingulate cortex and cognitive control: Neuropsychological and electrophysiological findings in two patients with lesions to dorsomedial prefrontal cortex. Brain and Cognition, 80, 237-249. doi:10.1016/j.bandc.2012.07.008