Hugh Garavan

Dissociable Executive Functions in the Dynamic Control of Behavior: Inhibition, Error Detection, and Correction

The present study employed event-related fMRI and EEG to investigate the biological basis of the cognitive control of behavior. Using a GO/NOGO task optimized to produce response inhibitions, frequent commission errors, and the opportunity for subsequent behavioral correction, we identified distinct cortical areas associated with each of these specific executive processes. Two cortical systems, one involving right prefrontal and parietal areas and the second regions of the cingulate, underlay inhibitory control. The involvement of these two systems was predicated upon the difficulty or urgency of the inhibition and each was employed to different extents by high- and low-absent-minded subjects. Errors were associated with medial activation incorporating the anterior cingulate and pre-SMA while behavioral alteration subsequent to errors was associated with both the anterior cingulate and the left prefrontal cortex. Furthermore, the EEG data demonstrated that successful response inhibition depended upon the timely activation of cortical areas as predicted by race models of response selection. The results highlight how higher cognitive functions responsible for behavioral control can result from the dynamic interplay of distinct cortical systems.

Insights into the neural basis of response inhibition from cognitive and clinical neuroscience

Neural mechanisms of cognitive control enable us to initiate, coordinate and update behaviour. Central to successful control is the ability to suppress actions that are no longer relevant or required. In this article, we review the contribution of cognitive neuroscience, molecular genetics and clinical investigations to understanding how response inhibition is mediated in the human brain. In Section 1, we consider insights into the neural basis of inhibitory control from the effects of neural interference, neural dysfunction, and drug addiction. In Section 2, we explore the functional specificity of inhibitory mechanisms among a range of related processes, including response selection, working memory, and attention. In Section 3, we focus on the contribution of response inhibition to understanding flexible behaviour, including the effects of learning and individual differences. Finally, in Section 4, we propose a series of technical and conceptual objectives for future studies addressing the neural basis of inhibition.

Executive Dysfunction in Cocaine Addiction: Evidence for Discordant Frontal, Cingulate, and Cerebellar Activity

Using a GO-NOGO response inhibition task in which working memory (WM) demands can be varied, we demonstrate that the compromised abilities of cocaine users to exert control over strong prepotent urges are associated with reduced activity in anterior cingulate and right prefrontal cortices, two regions thought to be critical for implementing cognitive control. Furthermore, unlike drug-naive controls, and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern previously seen in alcohol addiction. The results indicate that cocaine users find it difficult to inhibit their own actions, particularly when WM demands, which have been shown previously to increase during cue-induced craving for the drug, are increased. The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.

Executive Brake Failure following Deactivation of Human Frontal Lobe

In the course of daily living, humans frequently encounter situations in which a motor activity, once initiated, becomes unnecessary or inappropriate. Under such circumstances, the ability to inhibit motor responses can be of vital importance. Although the nature of response inhibition has been studied in psychology for several decades, its neural basis remains unclear. Using transcranial magnetic stimulation, we found that temporary deactivation of the pars opercularis in the right inferior frontal gyrus selectively impairs the ability to stop an initiated action. Critically, deactivation of the same region did not affect the ability to execute responses, nor did it influence physiological arousal. These findings confirm and extend recent reports that the inferior frontal gyrus is vital for mediating response inhibition.

Cingulate Hypoactivity in Cocaine Users During a GO-NOGO Task as Revealed by Event-Related Functional Magnetic Resonance Imaging

Although extensive evidence exists for the reinforcing properties of drugs of abuse such as cocaine, relatively less research has addressed the functional neuroanatomical correlates of the cognitive sequelae of these drugs. We present a functional magnetic resonance imaging study of a GO-NOGO task in which successful performance required prepotent behaviors to be inhibited. Significant cingulate, pre-supplementary motor and insula hypoactivity was observed for both successful NOGOs and errors of commission in chronic cocaine users relative to cocaine-naive controls. This attenuated response, in the presence of comparable activation levels in other task-related cortical areas, suggests cortical and psychological specificity in the locus of drug abuse-related cognitive dysfunction. The results suggest that addiction may be accompanied by a disruption of brain structures critical for the higher-order, cognitive control of behavior.

The functional neuroanatomical correlates of response variability: evidence from a response inhibition task

Intra-individual performance variability may be an important index of the efficiency with which executive control processes are implemented, Lesion studies suggest that damage to the frontal lobes is accompanied by an increase in such variability. Here we sought for the first time to investigate how the functional neuroanatomy of executive control is modulated by performance variability in healthy subjects by using an event-related functional magnetic resonance imaging (ER-fMRI) design and a Go/No-go response inhibition paradigm. Behavioural results revealed that individual differences in Go response time variability were a strong predictor of inhibitory success and that differences in mean Go response time could not account for this effect. Task-related brain activation was positively correlated with intra-individual variability within a distributed inhibitory network consisting of bilateral middle frontal areas and right inferior parietal and thalamic regions. Both the behavioural and fMRI data are consistent with the interpretation that those subjects with relatively higher intra-individual variability activate inhibitory regions to a greater extent, perhaps reflecting a greater requirement for top-down executive control in this group, a finding that may be relevant to disorders of executive/attentional control.

Serial attention within working memory

It is proposed that people are limited to attending to just one “object” in working memory (WM) at any one time. Consequently, many cognitive tasks, and much of everyday thought, necessitate switches between WM items. The research to be presented measured the time involved in switching attention between objects in WM and sought to elaborate the processes underlying such switches. Two experiments required subjects to maintain two running counts; the order in which the counts were updated necessitated frequent switches between them. Even after intensive practice, a time cost was incurred when subjects updated the two counts in succession, relative to updating the same count twice. This time cost was interpreted as being due to a distinct switching mechanism that controls an internal focus of attention large enough for just one object (count) at a time. This internal focus of attention is a subset of WM (Cowan, 1988). Alternative visual and conceptual repetition-priming and memory retrieval explanations for the cost involved in switching between items in WM are addressed.

A midline dissociation between error-processing and response-conflict monitoring

Midline brain activation subsequent to errors has been proposed to reflect error detection and, alternatively, conflict-monitoring processes. Adjudicating between these alternatives is challenging as both predict high activation on error trials. In an effort to resolve these interpretations, subjects completed a GO/NOGO task in which errors of commission were frequent and response conflict was independently varied by manipulating response speeds. A mixed-block and event-related fMRI design identified task-related, tonic activation and event-related activations for correct and incorrect trials. The anterior cingulate was the only area with error-related activation that was not modulated by the conflict manipulation and hence is implicated in specific error-related processes. Conversely, activation in the pre-SMA was not specific to errors but was sensitive to the conflict manipulation. A significant region by conflict interaction for tonic activation supported a functional dissociation between these two midline areas. Finally, an intermediate, caudal cingulate area was implicated in both error processing and conflict monitoring. The results suggest that these two action-monitoring processes are distinct and dissociable and are localised along the midline.

Multiple Neuronal Networks Mediate Sustained Attention

Sustained attention deficits occur in several neuropsychiatric disorders. However, the underlying neurobiological mechanisms are still incompletely understood. To that end, functional MRI was used to investigate the neural substrates of sustained attention (vigilance) using the rapid visual information processing (RVIP) task in 25 healthy volunteers. In order to better understand the neural networks underlying attentional abilities, brain regions where task-induced activation correlated with task performance were identified. Performance of the RVIP task activated a network of frontal, parietal, occipital, thalamic, and cerebellar regions. Deactivation during task performance was seen in the anterior and posterior cingulate, insula, and the left temporal and parahippocampal gyrus. Good task performance, as defined by better detection of target stimuli, was correlated with enhanced activation in predominantly right fronto-parietal regions and with decreased activation in predominantly left temporo-limbic and cingulate areas. Factor analysis revealed that these performance-correlated regions were grouped into two separate networks comprised of positively activated and negatively activated intercorrelated regions. Poor performers failed to significantly activate or deactivate these networks, whereas good performers either activated the positive or deactivated the negative network, or did both. The fact that both increased activation of task-specific areas and increased deactivation of task-irrelevant areas mediate cognitive functions underlying good RVIP task performance suggests two independent circuits, presumably reflecting different cognitive strategies, can be recruited to perform this vigilance task.

Amygdala response to both positively and negatively valenced stimuli

Human lesion and functional imaging data suggest a central role for the amygdala in the processing of negative stimuli. To determine whether the amygdalas role in affective processing extends beyond negative stimuli, subjects viewed pictures that varied in emotional content (positive vs negative valence) and arousal level (high vs low) while undergoing functional magnetic resonance imaging. Amygdala activation, relative to a low arousal and neutral valence picture baseline, was significantly increased for both positively and negatively valenced stimuli and did not differ for the two valences. There were no laterality effects. Whereas arousal level appeared to modulate the amygdala response for negative stimuli, all positively valenced pictures (both high and low in arousal) produced significant amygdala responses. These results clearly demonstrate a role for the amygdala in processing emotional stimuli that extends beyond negative and fearful stimuli.