Conflict processing in juvenile patients with neurofibromatosis type 1 (NF1) and healthy controls - Two pathways to success

Abstract

Neurofibromatosis Type 1 (NF1) is a monogenetic autosomal-dominant disorder with a broad spectrum of clinical symptoms and is commonly associated with cognitive deficits. Patients with NF1 frequently exhibit cognitive impairments like attention problems, working memory deficits and dysfunctional inhibitory control. The latter is also relevant for the resolution of cognitive conflicts. However, it is unclear how conflict monitoring processes are modulated in NF1. To examine this question in more detail, we used a system neurophysiological approach combining high-density ERP recordings with source localisation analyses in juvenile patients with NF1 and controls during a flanker task. Behaviourally, patients with NF1 perform significantly slower than controls. Specifically on trials with incompatible flanker-target pairings, however, the patients with NF1 made significantly fewer errors than healthy controls. Yet, importantly, this overall successful conflict resolution was reached via two different routes in the two groups. The healthy controls seem to arrive at a successful conflict monitoring performance through a developing conflict recognition via the N2 accompanied by a selectively enhanced N450 activation in the case of perceived flanker-target conflicts. The presumed dopamine deficiency in the patients with NF1 seems to result in a reduced ability to process conflicts via the N2. However, NF1 patients show an increased N450 irrespective of cognitive conflict. Activation differences in the orbitofrontal cortex (BA11) and anterior cingulate cortex (BA24) underlie these modulations. Taken together, juvenile patients with NF1 and juvenile healthy controls seem to accomplish conflict monitoring via two different cognitive neurophysiological pathways.

Keywords: Cognitive control; Conflict processing; EEG; Neurofibromatosis type 1; Source localisation.

Fig. 1

Event-related potentials (ERPs) (current source density) and topographic maps showing the (A) N2 and (B) N450 component during compatible and incompatible flanker trials for both groups. The time windows represented in the scalp topographies are stated in the methods section. Positive values are given in red, negative values are given in blue. Time point zero denotes the occurrence of the target stimulus. Negative values are plotted downwards. Inlays display sLORETA analyses. Plots show the difference between compatible and incompatible trials compared between the two groups. Colours denote t-values corrected using randomization tests.

Fig. 2

Event-related potentials (ERPs) (current source density) and topographic maps showing the flanker P1, flanker N1, target P1 and target N1 components during compatible and incompatible flanker trials for both groups. The time windows represented in the scalp topographies are stated in the methods section. Positive values are given in red, negative values are given in blue. Time point zero denotes the occurrence of the target stimulus. Negative values are plotted downwards.

Fig. 3

Event-related potentials (ERPs) (current source density) and topographic maps showing the P3 component during compatible and incompatible flanker trials for both groups. The time windows represented in the scalp topographies are stated in the methods section. Positive values are given in red, negative values are given in blue. Time point zero denotes the occurrence of the target stimulus. Negative values are plotted downwards.