Elsevier

Brain Research

Volume 1105, Issue 1, 11 August 2006, Pages 130-142
Brain Research

Research Report
Individual differences in the functional neuroanatomy of inhibitory control

https://doi.org/10.1016/j.brainres.2006.03.029Get rights and content

Abstract

We combined the data of five event-related fMRI studies of response inhibition. The re-analysis (n = 71) revealed response inhibition to be accomplished by a largely right hemisphere network of prefrontal, parietal, subcortical and midline regions, with converging evidence pointing to the particular importance of the right frontal operculum. Functional differences were observed between the sexes with greater activity in females in many of these cortical regions. Despite the relatively narrow age range (18–46), cortical activity, on the whole, tended to increase with age, echoing a pattern of functional recruitment often observed in the elderly. More absentminded subjects showed greater activity in fronto-parietal areas, while speed of Go trial responses produced a varied pattern of activation differences in more posterior and subcortical areas. Although response inhibition produces robust activation in a discrete network of brain regions, these results reveal that individual differences impact on the relative contribution made by the nodes of this network.

Introduction

Difficulty inhibiting inappropriate behaviours is characteristic of many psychological and psychiatric disorders ranging from the impulsivity of children with ADHD (Barkley, 1997), the loss of control exhibited by drug abusers (Fillmore and Rush, 2002, Kaufman et al., 2003), to the inappropriate stimulus-driven behaviour of brain-damaged individuals (Luria, 1966). Normal cognition is also subject to occasional inhibitory disruption as suggested by lapses in speech, action, thought and intention, wherein behaviour appears to be dictated by cue or by habit (Dempster and Brainerd, 1995). As a result of the apparent importance of this aspect of cognitive control, much effort has been expended in attempting to identify its neuroanatomical substrates. However, inhibitory control is a broad term incorporating cognitive (e.g., suppressing interference), perceptual/attention (e.g., ignoring distracters) and motor (e.g., response countermanding) domains. While the similarities and dissimilarities between these aspects of inhibition remain unclear (Bunge et al., 2002, Friedman and Miyake, 2004), it is the latter operationalisation that will be the focus here.

A substantial body of evidence on motor inhibition now exists due, in part, to the relative ease of implementing experimental tests of this function. Previous neuroimaging research has converged on a discrete number of regions thought to be implicated in motor response inhibition including dorsolateral and ventrolateral prefrontal cortex, parietal cortex, midline regions including the anterior cingulate and pre-SMA, and there is also evidence for thalamic and subcortical involvement (Aron and Poldrack, 2006, Brass et al., 2001, Braver et al., 2001, Garavan et al., 1999, Menon et al., 2001, Rubia et al., 2001, Watanabe et al., 2002). More specifically, ventral regions of the right hemisphere appear to be particularly important; the frontal operculum has been implicated by functional neuroimaging (Bunge et al., 2001, Konishi et al., 1998, Konishi et al., 1999), lesion data (Aron et al., 2003) and, more recently, by TMS studies (Chambers et al., 2006). A recent meta-analysis of Go/NoGo response inhibition studies confirms substantial right prefrontal activity, incorporating both dorsal and ventral regions (Buchsbaum et al., 2005).

While research appears to converge on a discrete network of regions central to inhibitory control, a somewhat contrary set of findings have demonstrated that the functional neuroanatomy of this function can differ across individuals and across circumstances. For example, the right lateralisation of inhibitory control appears to follow a developmental timecourse, with reduced activation levels in children aged between 8 and 12 relative to adults (Bunge et al., 2002) and increased bilateral activations in the elderly (Nielson et al., 2002). Such a developmental trajectory may reflect the emergence of cortical differentiation and its subsequent decline or, with regard to the greater bilaterality of function in elderly participants, may reflect a pattern of cortical recruitment (Cabeza, 2002). Within the same experiment, the pattern of inhibition-related activation can be seen to vary in response to changes in task demands (Kelly et al., 2004) or in response to a subject's ability to prepare for an impending response inhibition (Hester et al., 2004b).

Individual differences may also exist. Within other cognitive domains such as error processing, working memory or fluid intelligence, there is evidence that activation patterns can be affected by multiple factors such as individual differences in demographics (Hester et al., 2004a), basal levels of dopamine function (Gibbs and D'Esposito, 2005), hormone levels (Maki and Resnick, 2001), extent of task practice (Kelly and Garavan, 2005) or the cognitive strategies subjects employ (Braver et al., in press, Glabus et al., 2003, Speer et al., 2003). With regard to inhibitory control, subjects with more variable response times show greater inhibition-related activity in frontal, parietal and thalamic areas; variability in response times, independent of average response time, is a putative measure of sustained attention which correlates with inhibitory success (Bellgrove et al., 2004). Differences between subjects in the speed of the response countermanding process (the stop signal response time of the STOP task paradigm) have also been shown to correlate with the magnitude of inhibition-related prefrontal and subcortical activation (Aron and Poldrack, 2006).

It is of particular interest to determine if inhibitory control is affected by the sex of the individual. Many clinical conditions characterised by impaired impulse control are more prevalent in males than females. For example, a survey with over 9000 respondents revealed that men have a higher risk of impulse control and substance use psychiatric disorders (Kessler et al., 2005) while Attention Deficit and Hyperactivity Disorder (Neuman et al., 2005) and conduct disorder (Eme and Kavanaugh, 1995) are also more prevalent in males. Whether or not such disorders, which are multi-faceted and may have multiple causes, reflect inherent differences in how males and females implement inhibitory control is unknown. While there is evidence for brain function, brain volume and brain morphometry differences between the sexes (Haier et al., 2005, Luders et al., 2004, Jung et al., 2005, Shaywitz et al., 1995, Witelson et al., 2006), it is unclear if inhibitory control differences, if they exist, will be evident in functional brain differences as assayed by a cognitive task of response inhibition. A second demographic variable of interest, age, is also worth investigating as evidence already exists for age-related changes in the functional neuroanatomy of inhibitory control (Nielson et al., 2002). However, age changes presumably reflect developmental processes that are present throughout the lifespan rather than occurring at a threshold between “young” and “old”. Consequently, it is of interest to determine what age changes might occur within a younger age range.

Effective cognitive control requires a balance between the ability to proactively prepare (e.g., maintain task goals) and react (e.g., to an unexpected NoGo) to task circumstances. Deficiencies in either proactive or reactive control (Braver et al., in press) could account for poorer inhibitory performance: commission errors could arise from either an inability to actively attend to a task and maintain the response inhibition goal or a compromised ability to countermand an already initiated response. Previously, we have observed that those who score high on a measure of absentmindedness (Cognitive Failures Questionnaire, CFQ, Broadbent et al., 1982) showed reduced fronto-parietal activity but increased anterior cingulate activity for successful inhibitions (Garavan et al., 2002). A subsequent electrophysiological study observed larger and earlier N2 and P3 ERP components for successful inhibitions in those higher in absentmindedness (Roche et al., 2005). Combined, this suggests that absentmindedness may significantly affect inhibition-related activity levels, but it is unclear how exactly this individual difference may be realised. Finally, the functional neuroanatomy of response inhibition may be affected by the speed of Go response times. Faster responding on Go trials may increase the prepotency of responding and make inhibiting more difficult. Previously, we have shown this to be true on an intra-individual level but have not assessed inter-individual effects (Garavan et al., 2002).

On the whole, relatively little attention has been paid in the neuroimaging literature to individual differences, despite the sensitivity that neuroimaging techniques may have for revealing the cortical basis for differences. Pragmatic constraints, such as the costs associated with imaging sufficient numbers of subjects to enable an individual differences investigation, are one likely reason for this. Given this constraint, a meta-analysis (Buchsbaum et al., 2005) or a re-analysis of data combined from previous studies may be worthwhile strategies. To this end, this paper reports a re-analysis of five previous response inhibition studies that employed similar versions of an event-related Go/NoGo task. This approach, as well as providing robust statistical power for determining the functional neuroanatomy of inhibitory control, enables us to test for demographic effects on this neuroanatomy.

Section snippets

Performance measures

The relationship between demographic characteristics and behavioural performance was examined for the entire sample, indicating that none of the performance or demographic measures was significantly influenced by sex (see Table 1). Age showed a significant negative correlation with CFQ scores (r = −0.33, P ≤ 0.008), indicating that increasing age related to lower reported absentmindedness; Go RT significantly correlated with percentage of STOPS (r = 0.56, P < 0.0001), demonstrating that

Functional neuroanatomy of response inhibition

The present results reveal a distributed network of regions activated for successful response inhibitions. Motor response inhibition on this Go/NoGo task is largely accomplished by the right hemisphere with sizeable activations observed in fronto-parietal regions, in midline regions including the anterior cingulate and pre-SMA and in subcortical areas. Consequently, while it is perhaps safest to conclude that response inhibition is implemented by a network of regions, the challenge remains to

Subjects and task design

Seventy-one right-handed subjects (45 female, mean age 29, range: 18–46), reporting no history of neurological or psychological impairment, completed a Go/NoGo task after providing written informed consent. The initial design for the XY Go/NoGo task is described in Garavan et al. (1999), and slight modifications were made in four subsequent studies. In each study, subjects were presented with a serial stream of letters in which frequent Go stimuli (the letters X and Y) were presented in

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