Elsevier

Brain Research

Volume 1238, 31 October 2008, Pages 127-142
Brain Research

Research Report
Medial frontal cortex and response conflict: Evidence from human intracranial EEG and medial frontal cortex lesion

https://doi.org/10.1016/j.brainres.2008.07.114Get rights and content

Abstract

The medial frontal cortex (MFC) has been implicated in the monitoring and selection of actions in the face of competing alternatives, but much remains unknown about its functional properties, including electrophysiological oscillations, during response conflict tasks. Here, we recorded intracranial EEG during a modified Flanker task from the MFC of two patients undergoing pre-surgical evaluation for the treatment of epilepsy. Performance on the task was associated with a suppression of beta (15–30 Hz) frequency oscillation power prior to and just following the response and an enhancement of theta (4–8 Hz) frequency power following the response. Beta (theta) power was anatomically distributed towards more dorsal/caudal (rostral/ventral) electrode sites along the cortex, suggesting an anatomical/functional specialization along the medial frontal wall for pre-response versus post-response action monitoring. Inter-site phase coherence analyses demonstrated that the ventral/rostral MFC theta oscillations were coupled with theta oscillations observed at scalp electrodes Fz and Cz. One patient was tested before and after having epileptogenic tissue in the MFC surgically removed; task performance increased from chance levels to near-perfect, and an ERP conflict effect was observed only following surgery. These findings provide novel evidence for the role of MFC oscillations and their relation to surface EEG-recorded potentials during action monitoring.

Introduction

Adaptive and flexible behavior requires the ability to choose among multiple response options, often in the face of conflict or uncertainty. Although target monitoring and response selection engaged electrophysiological activity in several cortical and subcortical brain regions (Brazdil et al., 2005, Brazdil et al., 2002, Clarke et al., 1999, Rektor et al., 2003, Rektor et al., 2007, Roman et al., 2005), response conflict appears to engage specifically the dorsal cingulate and surrounding medial frontal cortex (MFC). This has been shown with functional MRI and EEG event-related potentials (Botvinick et al., 1999, Gehring and Knight, 2000, Lau et al., 2006, Nieuwenhuis et al., 2003, Ullsperger and von Cramon, 2001, van Veen and Carter, 2006, West et al., 2004). The precise neurocognitive mechanisms that these activations reflect remain debated. In brief, different theoretical accounts have proposed a role of the dorsal cingulate and surrounding MFC in terms of conflict monitoring, outcome evaluation [suggesting that MFC receives negative reinforcement signals to avoid actions that yield poor outcomes, Cohen et al., 2007, Holroyd and Coles, 2002)], risk prediction/error avoidance [suggesting that MFC serves to predict risk or error and promotes actions that lead to avoidance of risk and error, Brown and Braver, 2007, Ridderinkhof et al., 2004b)], cost-benefit analysis [suggesting that MFC serves action selection and decision-making through the estimation of outcome values based on reinforcement history, Rushworth et al., 2007], or regulative control [suggesting that MFC implements action control more directly, Matsumoto et al., 2003, Roelofs et al., 2006, Schall and Boucher, 2007]. Here we will term these MFC functions collectively as action monitoring, referring generally to its role in signaling and/or resolving situations in which performance must be monitored for potential risks or errors or conflicts that might otherwise interfere with the goals at hand.

Despite the wealth of research on the role of the MFC, several facets of its physiological functioning during response conflict tasks remain unknown, four of which are addressed here. First, the role of electrophysiological oscillations in response conflict remains largely unexplored, despite the fact that medial frontal oscillations have been linked to other processes, including memory, attention, and feedback processing (Basar-Eroglu and Demiralp, 2001, Brazdil et al., 2007, Cohen and Ranganath, 2007, Ishii et al., 1999, Kubota et al., 2001, Onton et al., 2005, Wang et al., 2005). Several studies have demonstrated that enhancements in medial frontal theta (4–8 Hz) power follow incorrect, compared to correct, responses (Gevins et al., 1997, Luu and Tucker, 2001, Luu et al., 2004, Trujillo and Allen, 2007, Yordanova et al., 2004), and one recent study found that ERPs following response conflict occur in theta and lower frequency bands, which increased in older and Parkinson's patients compared to controls (Schmiedt-Fehr et al., 2007). Whether this theta enhancement and activity in other frequency bands generalizes to situations of response conflict (e.g., prior to the response) has not, to our knowledge, been investigated.

A second issue that remains unknown is the relation between surface EEG potentials and local activity in the MFC. Surface EEG records activity from large swaths of cortex, and although mathematical point-source generator models have suggested that, consistent with functional MRI work, action monitoring effects might be generated by tissue in the dorsal cingulate cortex or surrounding MFC (Alain et al., 2002, Holroyd et al., 1998, Wills et al., 2007), these are indirect evaluations and not direct measurements of deep brain activity. Further, the intracranial sources of medial frontal theta have been speculated to originate in the dorsal cingulate cortex and surrounding MFC (Cohen and Ranganath, 2007, Luu et al., 2004), although this has not been verified in humans. Although functional MRI has better spatial resolution than surface EEG, it has neither the temporal resolution nor capability to measure neural oscillations and neurocognitive processes that change rapidly over time. Further, results from functional MRI do not always match those of intracranial EEG (Brazdil et al., 2005). Thus, recording electrophysiological activity directly from the MFC in the human may shed light onto the neural generators of surface-recorded ERP conflict-related potentials.

The third issue addressed here relates to anatomical/functional dissociations of regions within the MFC. Activity in many cortical regions dissociates correct from incorrect responses (Brazdil et al., 2002), although the medial frontal wall appears to play a prominent role (Carter and van Veen, 2007, van Veen and Carter, 2006). Within the medial frontal wall, meta-analyses of the literature suggest an anatomical division of labor, such that more dorsal/caudal regions (e.g., Brodmann area [BA] 8 and pre-SMA) are sensitive to pre-response conflict or uncertainty, whereas more rostral regions are sensitive to errors and post-response monitoring (e.g., BA 24) (Ridderinkhof et al., 2004b, Ullsperger and von Cramon, 2001). Both intracranial EEG and functional MRI could provide insight into possible anatomical/functional dissociations, but only intracranial EEG can uncover the electrophysiological oscillatory processes—and differences in oscillatory characteristics—in different regions.

Finally, we tested whether and how a lesion in part of the MFC would affect task performance and associated ERPs. Previous studies have demonstrated that lesions in the anterior cingulate lead to an attenuated error-related negativity (Swick and Turken, 2002), and impaired ability to adjust behavioral control following high conflict (di Pellegrino et al., 2007). Further, lesions of the lateral prefrontal cortex lead to reduced error-related negativities (Gehring and Knight, 2000). Here we examined whether performance in a conflict task and associated ERPs would be affected by the resection of epileptic tissue in MFC. Note that lesion studies of humans with epileptogenic foci are not necessarily comparable to lesion studies in animals or in humans with damage to healthy tissue (e.g., injury from an accident). This is because in animals and humans with natural injuries, lesioned tissue was previously healthy, and thus making appropriate functional contributions to cognition. In contrast, epileptogenic tissue is more or less dysfunctional, and thus may contribute aberrant activity that can impair cognition. Indeed, focal resection of epileptic tissue can sometimes improve cognitive performance (Leijten et al., 2005, Lendt et al., 2002, Sanyal et al., 2005), perhaps due to neural functional reorganization or a reactivation of functions previously suppressed by influence of epileptogenic areas (Elger et al., 2004).

Intracranially recorded EEG provides a rare opportunity to understand the functions of the human cortex with better spatial precision than surface EEG, and with better temporal resolution than functional MRI. Further, the increased signal-to-noise ratio compared to surface EEG allows for reliable results from a small number of patients. Thus, to investigate the issues delineated above, we conducted a variant of the Flanker task with two patients who had electrodes implanted in the MFC, including dorsal and caudal, as well as more ventral/rostral, portions of the anterior cingulate cortex and superior frontal gyrus (spanning BA 6, 8, 24, and 32), as part of pre-surgical evaluation for the treatment of epilepsy (Fig. 1). One patient subsequently had part of the MFC surgically resected, providing the opportunity to examine changes in behavioral performance and surface electrophysiology pre- and post-surgical removal of part of the medial frontal wall. We focus our analyses on task-induced oscillations and how neural processes recorded at focal sources relate to activity recorded over the scalp. With respect to the three aspects of the neurocognitive functions of the MFC, considered above, we expect (1) to observe enhancements of oscillatory power in theta and perhaps other frequency bands during action monitoring; (2) to confirm that ERP and oscillatory patterns recorded from surface EEG correspond (functionally and temporally) to those recorded directly from intracranial sources in the MFC; and (3) to establish whether pre- versus post-response conflict is represented by electrophysiological oscillations in different frequency bands and anatomical locations. These findings provide novel insights into the neural mechanisms of action monitoring, and increase our understanding of the neurocognitive functions of the MFC during flexible, goal-directed behavior (Fig. 1).

Section snippets

Behavioral performance

RK performed quite well at the task (Fig. 2b). Accuracy was 97% for congruent trials and 98% for incongruent trials. RTs increased for incongruent compared to congruent trials, from 726 to 852 ms (std: 154/157; p < 0.001, obtained by boot-strapping; see Experimental procedures). We did not analyze reaction times for incorrect trials because there were so few errors (these trials were not included in the behavior or EEG analyses). We also analyzed whether these effects were dependent on whether

Discussion

Here we examined the behavioral performance, intracranial and surface electrophysiology of two patients who had electrodes implanted along the inner wall of MFC. The modified Flanker task was successful at inducing response conflict, evidenced by the increased RTs for incongruent conditions. Patient RK performed quite well at the task. Interestingly, patient AP performed better following surgery compared to before surgery, although RTs suggested that she was sensitive to the conflict

Patients

Two patients with pharmacoresistant epilepsy (both women; aged 17 [AP] and 53 [RK]) participated in the study. Recordings were performed at the Department of Epileptology, University of Bonn, Germany. No seizure occurred in either of the patients during the 24 h preceding the experiment. The location of electrode placement was made entirely on clinical grounds (see Fig. 1). Patient RK suffered from a cryptogenic epilepsy with single-focal seizures and hypomotoric complex-focal seizures. The MRI

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