Error-related processing following severe traumatic brain injury: An event-related functional magnetic resonance imaging (fMRI) study

Abstract

Continuous monitoring of one's performance is invaluable for guiding behavior towards successful goal attainment by identifying deficits and strategically adjusting responses when performance is inadequate. In the present study, we exploited the advantages of event-related functional magnetic resonance imaging (fMRI) to examine brain activity associated with error-related processing after severe traumatic brain injury (sTBI). fMRI and behavioral data were acquired while 10 sTBI participants and 12 neurologically-healthy controls performed a task-switching cued-Stroop task. fMRI data were analyzed using a random-effects whole-brain voxel-wise general linear model and planned linear contrasts. Behaviorally, sTBI patients showed greater error-rate interference than neurologically-normal controls. fMRI data revealed that, compared to controls, sTBI patients showed greater magnitude error-related activation in the anterior cingulate cortex (ACC) and an increase in the overall spatial extent of error-related activation across cortical and subcortical regions. Implications for future research and potential limitations in conducting fMRI research in neurologically-impaired populations are discussed, as well as some potential benefits of employing multimodal imaging (e.g., fMRI and event-related potentials) of cognitive control processes in TBI.

Introduction

Physical and neurobehavioral impairments are common sequelae of traumatic brain injury (TBI; Horn and Sherer, 1999), however, even in patients with good neurological recovery, persistent cognitive deficits are among the most pronounced and frequent complaints of TBI survivors (Cicerone et al., 2005, Lovell and Franzen, 1994). Severity-related impairments in “cognitive control,” a set of higher-order executive processes supported by the prefrontal cortex and critical to executive function (Lorist et al., 2005, Miller, 2000, Miller and Cohen, 2001), are thought to underlie some aspects of enduring cognitive dysfunction after brain injury (Larson et al., 2006, Larson et al., 2007a, Larson et al., in press, Perlstein et al., 2004, Perlstein et al., 2006, Scheibel et al., 2007, Seignourel et al., 2005, Soeda et al., 2005), and current theories of neurobehavioral dysfunction in TBI have been based on observed impairments in cognitive control component processes (Anderson et al., 2002, Burgess and Robertson, 2002, Larson et al., 2006, Larson et al., 2007a, Levine et al., 2002, Perlstein et al., 2006).

Numerous functional magnetic resonance imaging (fMRI) studies (i.e., Carter et al., 1999, MacDonald et al., 2000) suggest that cognitive control comprises two broad component processes implemented in a closely interactive, yet dissociable frontal neural network: a regulative/strategic component supporting the maintenance of task goals, allocation of limited attentional resources, and the implementation of top-down control (MacDonald et al., 2000), and an anterior cingulate cortex (ACC)-mediated evaluative component that supports conflict processing and performance monitoring (i.e., Carter and van Veen, 2007, Kerns et al., 2004, van Veen and Carter, 2002, van Veen and Carter, 2006). These evaluative monitoring processes serve to adjust behavioral performance toward goal attainment based on the detection of performance errors (Ridderinkhof et al., 2004). Continuous performance monitoring is important for guiding behavior towards successful goal-attainment by detecting deficiencies and strategically adjusting responses when current performance is inadequate. An understanding of the neural basis underlying error-related processing is critical not only to identifying the mechanisms through which cognitive control is executed, but also because impairments in self-awareness in TBI patients may partially arise from impaired performance-monitoring abilities (Larson and Perlstein, 2009, O'Keeffe et al., 2004).

Whereas numerous studies of impaired executive function following brain injury have focused their attention on examining the impairment of top-down regulative processes of cognitive control that rely heavily on the dlPFC (i.e., Christodoulou et al., 2001, Larson et al., 2006, McAllister et al., 2001, Perlstein et al., 2004, Perlstein et al., 2006, Seignourel et al., 2005), research examining the impairment of performance monitoring functions of cognitive control, or the potential role that alterations in ACC function contribute to cognitive dysfunction after brain injury is limited (i.e., Larson et al., 2007a, Scheibel et al., 2003, Soeda et al., 2005). Importantly, available neuroimaging and electrophysiological findings from studies conducted both in- and-outside of our laboratory have provided evidence demonstrating alterations in ACC-mediated evaluative activity in TBI patients. Specifically, electrophysiological studies have demonstrated that TBI patients display attenuated scalp-recorded event-related potential (ERP) components thought to reflect ACC-mediated evaluative monitoring aspects of control including the conflict-related N450 (Perlstein et al., 2006), error-related negativity (ERN; Larson et al., 2007a, Stemmer et al., 2004), and feedback-related negativity (FRN; Larson et al., 2007b). Similarly, alterations in ACC-mediated evaluative activation have also been observed using fMRI, however, results have been contradictory. For example, Soeda et al. (2005) observed reduced ACC activation in TBI patients during completion of a modified Stroop task that elicited a high degree of response conflict, Scheibel et al. (2007) observed greater ACC activation in TBI patients during completion of a stimulus-response compatibility cognitive control task. Findings from both studies (Scheibel et al., 2007, Soeda et al., 2005) suggest that neural networks mediating cognitive control and evaluative processes of control are disrupted after brain injury; however, these findings do not account for error-related activity, and methodological limitations (i.e., use of blocked fMRI designs) in the studies described above also preclude full interpretation of results.

In the present study, we build upon available research findings and address the methodological limitations described above by exploiting the advantages of event-related fMRI which enables us to separately evaluate correct- and incorrect-trial response activity and, therefore, to examine potential alterations of activity reflecting error-related processing after TBI. Specifically, we tested the hypothesis that in comparison to healthy controls, patients with severe TBI (sTBI) would show smaller magnitude error-related activation of the ACC during completion of a cued-Stroop task, a cognitive task that has been found to reliably elicit a high degree of cognitive control and response conflict (Kerns et al., 2004, West, 2003).