Sustained Attention, Alertness and Arousal

Sustained Attention, Alertness and Arousal 1 Vigilant Attention Ian H Robertson and Hugh Garavan Department of Psychology and Institute of Neuroscience Trinity College Dublin, Ireland Robertson IH and Garavan H (2004) Vigilant Attention. In M. S. Gazzaniga The Cognitive Neurosciences, 3rd edition. Michael S. Gazzaniga Editor-in-Chief. MIT Press November 2004, 563-578. 1 Robertson and Garavan 2 Abstract When train drivers pass through warning or stop signals – as they do many thousands of times per day throughout the world – this is an example, we argue, of an inefficiency in the functioning of a right hemispheric, fronto-parietal attention system for „vigilant attention?. Closely linked to Posner?s notion of the „alerting? system, vigilant attention is distinct from Posner?s other two functionally and anatomically distinct supramodal attentional systems – selection and control respectively. We review evidence for the validity of this 3-factor typology of attention, and clarify the frequently articulated misconception that „vigilance? and „sustained attention? are defined by time-on-task decrements over extended periods of test performance, as originally proposed by Mackworth. Rather, we show that vigilant attention involves a half-life measured in seconds rather than minutes, and is most sensitively measured in situations where routine action cycles are under way. We further show evidence of how everyday action error propensities link to specific functional brain activation patterns and how Attention Deficit Disorder can be an excellent model system for malfunctioning of this system. We end by demonstrating the possibilities for rehabilitation of this system. 2 Robertson and Garavan 3 A neglected dimension of attention thAt 24 minutes past 5 on the 8 August 1996, the 17.04 train from London?s Euston Station to Milton Keynes passed through a red signal near Watford Junction and ploughed into an empty goods train, killing just one person - Ruth Holland - associate editor of the British Medical Journal and a close colleague of the first author of this chapter. The driver of the train, Peter Afford, was later cleared of criminal charges for having passed the red signal; the court accepted his defence that trees and bushes had obscured the signal. He also told the court that he could not remember seeing two early warning signals that would have told him to expect a red light at the next signal point. Signals passed at danger (SPAD) is the most common cause of accidents on railways (Edkins and Pollock, 1997) and imperfectly sustained attention is by far the major factor in these errors. Every day, thousands of signals are passed at danger by train drivers worldwide, but thankfully only a small number result in tragedy – partly through good fortune and partly through the presence in some railway systems of other backup safety measures. This type of error is classified as a skill-based slip that typically occurs during routine action sequences (Reason, 1992). The job of driving a train is typically routine, stopping at stations and travelling sections of track that the driver has passed many times before. Familiar surroundings and well-practised sequences of actions minimise the need for effortful attention on the part of the driver. The focus of the current chapter is that type of attentional control that is crucially required for error-free performance of this type of task. This type of attention is linked to a number of hitherto ambiguously defined concepts such as vigilance, alertness, sustained 3 Robertson and Garavan 4 attention and arousal. We will use the term „vigilant attention? to characterise this in the present chapter. Among the first studies of vigilant attention to be carried out were those by Mackworth and his colleagues at the MRC Applied Psychology Unit in Cambridge, UK. These were particularly inspired by the problems encountered by operators of the recently developed radar, who had to maintain attention to a small, dim and mostly unchanging screen, for rare but crucially important events – enemy or about-to-collide aircraft. This research concluded that it was often difficult to pull human observers off ceiling on this type of vigilance task and that errors, when they did occur, were only observed over relatively long time periods approaching – usually more than 30 minutes (Mackworth, 1968; Mackworth, 1950). The difficulty in finding sensitive measures of vigilant attention, as demonstrated by these contemporary measures, may have been one factor that led to its relative neglect for the next 30 years, in comparison, that is, to the burgeoning research in other major aspects of attention linked to selection, working memory and switching. A second reason for its demise as a major subject of research may have been the loss of confidence in the unitary nature of its sister process – arousal. The classic studies of Moruzzi and Magoun (Moruzzi and Magoun, 1949) suggesting the existence of a single arousal-modulating reticular formation gave way to evidence for the existence of multiple ascending pathways from subcortical nuclei, each linked to different neurotransmitters and different cortical innervation (Olszewski and Baxter, 1982). The resurrection of vigilant attention as an important dimension of attention is due largely to the work of Michael Posner (Posner and Boies, 1971) and Raja Parasuraman (Parasuraman, 1983) with the onset of human functional brain imaging providing a major 4 Robertson and Garavan 5 boost to the validity of their typologies of attention (Posner and Peterson, 1990). Posner and colleagues suggested the existence of three main functionally and anatomically distinct types of supramodal attentional control systems - selection, orientation and alertness. This was somewhat different from Posner and Boies earlier typology – selection, capacity and alertness, but close to Parasuraman?s typology of selection, control and vigilance (Parasuraman, 1998). The important aspect of these typographies, however, is the clear distinction between attention as selection/management of goals in working memory on the one hand versus attention as vigilant attention linked to alertness on the other. It is the latter of these two dimensions that we focus on in the current chapter. The restless brain: Why doing little is so hard If vigilance is such a fundamental dimension of attention, why is it relatively difficult to show decrements on standard vigilance tasks in normal human adults? Mackworth?s would-be radar operators in a darkened room often performed normally for an hour or longer before they began to show the vigilance decrement that was seen to be the hallmark of this attentional system. Even in people with traumatic brain injury and consequently impaired frontal lobe/attentional deficits, marginal decrements could only be observed in sustained attention when the visual stimuli were heavily perceptually degraded (Parasuraman et al., 1991). Responding to infrequent target versus inhibiting ongoing behaviour Why should train drivers frequently miss danger signals while participants in vigilance experiments show such good performance? A possible answer to this question may be that, unlike the radar operators who must make a response to rare targets, train drivers 5 Robertson and Garavan 6 must inhibit their ongoing behaviour in the context of a rare target – namely a red or warning signal. When required to make a response, the presentation of the rare target can facilitate performance insofar as (a) the default response in a task such as this is not to respond thereby providing time to detect the target and make the appropriate response and (b) the presentation of the rare target can itself serve to orient attention to its presence. Contrast this with the circumstance in which people must inhibit responding to rare stimuli. Here, the ongoing default behaviour (responding, or in the case of the train driver, to keep driving forward) is opposite to the desired response (i.e., interrupt the default behaviour). Furthermore, the ongoing behaviour which engages the person in well-practiced behaviours can create the illusion that the person is attentively engaged in the task at hand. However, the automatic quality of the behaviour can be deceptive as it, in fact, requires little vigilant attention. Consequently, the commission error might be committed before the person can countermand it or, as in the train driver, without the person even noticing that the countermand was required. This distinction between responding and inhibiting also rests on whether the vigilant attention for the task must be generated endogenously or is supported by exogenous task demands, an important issue that will be addressed later. This distinction can be seen clearly when you compare frontally- and attentionally-impaired traumatic brain injury patients with controls on a task that requires detection of rare targets with one which requires inhibition of response to rare targets – the latter being more closely analogous to the train driver situation (Robertson et al., 1997a). In this study, controls and traumatic brain injured patients made statistically indistinguishable numbers of errors when they had to detect rare (11%) targets - 6 Robertson and Garavan 7 ascending or descending trios of digits (eg 234 or 987 in an otherwise random stream of one-per-second digits). Yet the frontally-impaired patients did show significant impairment – twice the error rate of controls – on a task where they had to withhold a response to the number 3, also appearing 11% of the time in the same stream of randomly appearing digits (Sustained Attention to Response Task – SART). We believe these deficits result from a dynamic interaction between inhibitory abilities and vigilant attention as becomes apparent when we made the sequence of digits entirely predictable – 1,2,3,4,5,6,7,8,9,1,2,3 … etc. Whereas normal controls make only occasional errors on this task, TBI patients have considerable difficulty and in one study made more than 7 out of 25 errors – 28% - despite there being a totally predictable sequence leading up to the target letter (Manly et al., in press-b)(see figure 1). Here, the inability to withhold responding is likely due to an inability to maintain a sufficient level of arousal and a sufficiently strong representation of the task goals (“don?t respond to 3”): when vigilant attention is poor, the patient defaults to the frequent response. Later we will expand on these two central components of vigilant attention, arousal and goal representation. Figure 1 about here Exogenous versus endogenous modulation of vigilant attention As we will discuss later in the section on arousal, vigilant attention can be impaired through administration of drugs – for instance clonidine - that inhibit noradrenaline release. One study, for example (Smith and Nutt, 1996), confirmed that noradrenaline suppression in humans led to vigilant attention lapses but they also showed that this effect was much attenuated when the participants were exposed to loud white noise while performing the task. This suggests that external stimuli can induce „bottom-up? or 7 Robertson and Garavan 8 exogenous modulation of the cortical systems for vigilant attention. Coull and her colleagues confirmed that this is indeed the case (Coull et al., 1995b); (Coull et al., 1995a), showing that clonidine-induced noradrenergic suppression impaired vigilant attention performance much more when the task was familiar than when it was unfamiliar. Furthermore, other research by Arnsten and Contant ((Arnsten and Contant, 1992)) showed that the clonidine affected delayed response performance during a delay period less when a distractor was interpolated in the delay period than when the period was free of distractors. This apparently paradoxical effect where the deleterious effect of a drug is reduced by making the task more difficult is a key finding in understanding how the vigilant attention system might function. What these findings suggest is that this system can be engaged by both endogenous and exogenous means; furthermore, where exogenous activation takes place, we argue, this considerably reduces the demands on the endogenous components of the system. But do exogenous and endogenous input activate the system in the same way? One of our recent studies suggest that this may not be the case. In a recent fMRI study of the SART (O'Connor et al., in press-b) we showed that, compared to a rest period, the standard SART (press to digits, except to randomly appearing, 11% frequency, 3?s) showed precisely the right fronto-parietal activation that we would predict as being needed for a task that placed demands on the vigilant attention system. We had previously shown, however, that performance on SART and on other tasks requiring vigilant attention could be much enhanced by presenting non-informative auditory arousing tones randomly during task performance (Manly et al., 2002; Manly et al., in press-a). On the basis of these data, we predicted that these exogenous stimuli 8 Robertson and Garavan 9 externally activated vigilant attention, hence reducing the demands on the endogenous components of that system that we argue are based in the right hemisphere fronto-parietal system. What we in fact found was that presenting alerting tones during SART did eliminate the right frontal activation, but did not eliminate the right parietal activation. In other words, it seems as if the parietal component of the right hemisphere vigilant attention system may be a common pathway for both endogenous and exogenous routes, while the right frontal element may be particularly linked to endogenous activation. We have also shown that increasing the task demand in the SART paradoxically reduces the proportional number of errors of commission. When the inhibit target is relatively rare – 11% - proportionately more errors are made than when the target is more common – 25% - and the proportional error rate declines linearly as the target rate increases to 50% (Manly et al., 1999) (see figure 2a). Furthermore, self-reported proneness to everyday attentional slips - such as forgetting why one has walked into a room (as measured by the cognitive failures questionnaire (Broadbent et al., 1982)- are significantly related to the proportion of errors made on the 11% target frequency SART, but not where the targets are more frequent (see figure 2b) (Manly et al., 1999). We interpret these effects as being due to the repeated targets in the higher frequency condition providing increased exogenous support for the task through repeated activation of the “inhibit response” motor action and goal representation. We believe that one feature of tasks sensitive to the vigilance system is that this type of exogenous support is absent or relatively weak and consequently the vigilance system must be maintained endogenously, a function for which the right prefrontal areas appear especially important. Figure 2 a and b about here 9 Robertson and Garavan 10 Attention and Arousal What is ‘arousal’? Arousal has been defined as „…some level of non-specific neuronal excitability deriving from the structures formerly known as the reticular formation but now generally referred to as specific chemically defined or thalamic systems that innervate the forebrain? (Robbins and Everitt, 1995). This definition rescues the concept of arousal from doubts about its unitary nature that followed the original identification of this function with the reticular formation (Moruzzi and Magoun, 1949). This identification was based in part on the finding that electrical stimulation of this subcortical region elicited behavioural arousal and EEG desychronisation characteristic of the alert state. Furthermore, lesions to this region caused coma, and these and other findings led to the concept of the midbrain reticular formation and associated structures as a key system for regulating cortical arousal. Subsequent research however showed that a number of neuroanatomically and neurochemically distinct systems projected to various parts of the cortex from different subcortical nuclei including the cholinergic basal forebrain, the noradrenergic locus coeruleus, the dopaminergic median forebrain bundle and the serotinergic dorsal raphe nucleus. Understandably, confidence in a single construct of „cortical arousal? was considerably weakened by these findings (Olszewski and Baxter, 1982). Human functional brain imaging helped revive the flagging concept of arousal as a useful explanatory heuristic. Kinomura, Paus and their colleagues identified the midbrain reticular formation and the intralaminar and other thalamic nuclei with arousal (Kinomura et al., 1996; Paus et al., 1997). Both Paus (Paus et al., 1997) and Critchley (Critchley et al., 2001; Critchley et al., 2002) have proposed that the anterior cingulate 10 Robertson and Garavan 11 plays a key role in regulating arousal in response to task demands, thereby providing neuroanatomical guidance on how the vigilant attention system might interface with subcortical arousal mechanisms. The extensive connectivity between fronto-parietal areas and the cingulate may enable the communication between these two systems. Electrophysiological measures have also continued to generate data that confirm the utililty of – for heuristic purposes at least – accepting the existence of arousal as a viable concept. In the Paus et al PET study cited earlier, for instance, the decline in sustained attention over time was associated not only with a decline in metabolic activity in the right hemisphere cortical and subcortical regions already described, it was also correlated with an increase in low-frequency activity in the EEG spectrum. A further study (Makeig and Jung, 1995) showed that vigilance errors were linked to short-term changes in the EEG spectrum, and these changes correlated with concurrent changes in level of performance on a sustained auditory detection task. This author concluded: "…the one- dimensional relationship between detection performance and the EEG spectrum confirms quantitatively the intuitive assumption that minute-scale changes in behavioral alertness during drowsiness are predominantly linked to changes in global brain dynamics along a single dimension of psychophysiological arousal" (p 213). While it is outwith the scope of this chapter to review the neurochemistry of arousal, a number of authors ((Berridge and Waterhouse, 2003; Posner and Peterson, 1990; Usher et al., 1999)) make a strong case for a particularly close linkage between vigilant attention on the one hand, and the activity of the noradrenergic system on the other. Animal research shows, for instance, that locus coerulus activity is higher when animals are observed as being behaviourally alert (Aston-Jones et al., 1991). Furthermore the 11 Robertson and Garavan 12 appearance of a low-probability target among foils leads to increased LC activity and widespread noradrenergic release (Berridge and Waterhouse, 2003). As will be seen below, the relationship is likely more complex than this, but the evidence of a close linkage between noradrenergic activity and vigilant behaviour is strong. This is particularly true given the evidence, cited earlier, that in humans, reducing noradrenaline release through clonidine administration results in the sorts of attentional lapses characteristic of states of poor alertness/sustained attention (Smith and Nutt, 1996). There is some evidence also that noradrenaline may have a stronger right than left hemisphere innervation (Oke et al., 1978; Robinson, 1979), giving further support to a particularly close relationship between the vigilant attention system and noradrenaline activity. While the cholinergic system is also involved in vigilant attention (Sarter et al., 2001) it is the evidence for noradrenergic right hemispheric lateralisation combined with the clear right hemisphere dominance for vigilant attention that lead many authors to postulate a particular linkage between noradrenaline and vigilant attention. Links between Attention and Arousal In 1908, Robert Yerkes and John Dodson studied the effects of different degrees of arousal (by varying degree of shock) in mice on their ability to learn discriminations between the luminance of two compartments (Yerkes and Dodson, 1908). They found that where lightness levels were easily discriminated, the mice performed better at high levels of arousal, whereas difficult light discriminations were best learned at low levels of arousal. On the basis of these experiments, they formulated the Yerkes-Dodson law. This law proposed that any task will have an optimal level of arousal below and beyond which performance will decline; this optimal level is lower in challenging tasks than in routine 12 Robertson and Garavan 13 tasks, they hypothesised. Similarly, Donald Broadbent showed that stress can improve performance on routine, non-demanding tasks, but the same levels of stress can impair performance on more complex and demanding tasks (Broadbent, 1971). These classical psychological studies suggesting an interaction between arousal levels, optimal performance, and degree of challenge in a task mesh well with the notion of exogenous modulation of arousal as previously discussed. It also suggests, however, that the relationship between the system for vigilant attention and arousal may not be a simple one of mutual facilitation, and a number of other more recent studies support such a view. Progress has been made in identifying the neuroanatomical basis for this attention-arousal coupling. For example, locus coeruleus (LC) activity has been show to correlate closely with behavioural performance where monkeys have to detect relatively rare (20% probability) visual targets among foils, but optimal performance was achieved not at maximum levels of locus coeruleus activity, but rather at intermediate levels (Usher et al., 1999). Increased tonic LC noradrenergic activity was linked to decreased reponsivity of LC neurons to target stimuli, as well as to poor behavioural performance. These authors proposed that high tonic LC activity offers a mechanism for sampling new stimuli and behaviours by decreasing attentional selectivity and increasing the behavioural responsiveness to unexpected or novel stimuli. Intermediate levels of tonic LC activity, on the other hand, allow the optimising of performance in a stable environment. In a comprehensive review of catecholamine modulation of prefrontal cognitive function, Arnsten showed that many studies have confirmed the findings of Usher et al, in showing a Yerkes-Dodson type inverted-U relationship between levels of noradrenalin release on the one hand, and behavioural performance on the other (Arnsten, 1998). She also 13 Robertson and Garavan 14 concludes that different neuropsychiatric conditions may reveal impairment in executive control of complex behaviours for reasons of either deficient or excessive levels of noradrenaline respectively. The study mentioned earlier by Paus and colleagues (Paus, Zatorre, Hofle, Caramanos, Gotman, Petrides et al., 1997) demonstrated the inter-relatedness of attention and arousal. To recap, in this study healthy participants were asked to perform a simple vigilance task for around 60 min. Every 10 min, regional cerebral blood flow and EEG were measured. Significant reductions in blood flow were observed in subcortical structures, the thalamus, substantia innominata and putamen, and in right hemisphere cortical areas, including frontal and parietal cortex. These were interpreted by the authors as a subcortical arousal system and right cortical attentional system, respectively. Increases in low theta activity, associated with reduction in arousal, were also observed on the EEG as the task progressed. Despite the reduction in blood flow in the right hemisphere based “attentional” and subcortical “arousal” networks, the number of successful target detections did not significantly decline over the hour of the task. This was interpreted as reflecting a need for active attentional engagement early on in the task which declined as target detection became increasingly automatic. Results such as these suggest that the term “sustained attention” may be somewhat inappropriately applied to situations which clearly require sustained performance but which may actually make relatively limited demands on what might be termed vigilant attention. This distinction is perhaps best captured by consideration of whether “maintaining” responsivity to an arbitrary but overlearned stimulus such as one?s own name requires anything approaching an active maintenance of attention at all. 14 Robertson and Garavan 15 Such a conclusion would be supported by Coull et al (Coull et al., 1996) who also found declines in thalamic and right fronto-parietal perfusion over an 18 minute task period in which participants had to respond whenever any letter appeared on the screen, and these stimuli appeared on average every 20 seconds, with a range of 10-30 seconds. In contrast, when the task was made a relatively difficult selective attention task by requiring participants to respond only to red B's interspersed among red and blue B's and G's , no significant decline in the right frontal and parietal cortices was observed. This is in line with the earlier arguments about the effects of exogenous demand on vigilant attention, and suggests that this right fronto-parietal system for vigilant attention is - in part at least - a system needed to maintain alert and reasonably accurate responding in the absence of strong external demands or stimuli that otherwise 'support' alert responding. Assuming this to be the case, then a major role of the right fronto-parietal system is to modulate arousal, particularly where that arousal is not externally generated by task demand or stimulus. As mentioned earlier, the anterior cingulate may serve on the interface between cognition and emotion and may serve as a conduit by which the right prefrontal-parietal system modulates arousal levels. This appearance of a functional wood from out of the neurochemical trees allows us to begin to develop the concept of a broad mesencephalic arousal system operating in concert with a predominantly right hemisphere fronto-parietal vigilant attention system. What distinct contributions the right prefrontal and right parietal structures might make to vigilant attention is the topic to which we will next turn. Fronto-parietal interactions in vigilant attention 15 Robertson and Garavan 16 The right dorsolateral prefrontal and inferior parietal cortices of the right hemisphere have been widely implicated in vigilant attention, as we have demonstrated over the last several pages. One possibility is that the right prefrontal cortex may have a particular role in the endogenous components of this system, while the inferior parietal cortex may be commonly activated by both endogenous and exogenous pathways. We have shown that the effects of exogenous alerting stimuli on performance on the SART, described earlier (O'Connor et al., in press-a) were to reduce neuronal activity in the right prefrontal cortex, but not in the right inferior parietal cortex. A recent meta-analysis of error-related activations (n=44) from a number of our event-related GO/NOGO response inhibition tasks similar in structure to the SART has revealed robust right inferior parietal lobule activation that correlated negatively with the numbers of errors subjects committed. We have consistently seen this parietal area and right dorsolateral prefrontal cortex co-activated during response inhibition (Garavan et al., 1999; 2002). The presence of the parietal activation for both errors and successful inhibitions suggests that it has a more general attentional role in processing the salient NOGO stimuli and not in response inhibition per se, while the negative correlation suggests that greater activation here is associated with better performance. The right prefrontal area is probably critical to the response selection process itself (Garavan et al., 2002; Garavan et al., 1999) (Rowe et al., 2000). Combined, these disparate findings suggest that the right inferior parietal cortex has a role in the routine, semi-automatic maintenance of sustained vigilant responding, whereas the right dorsolateral prefrontal cortex has a more "executive" role in maintaining the vigilant state. One hypothesis for what this executive role involves might be to 16 Robertson and Garavan 17 engage/initiate the vigilant state based on a dynamic assessment of the optimal arousal level to match performance to task demands. This implies that the monitoring of either one's endogenous arousal levels or of one's performance is information crucial for the functioning of the vigilant attention system. This monitoring function might be performed by the right prefrontal area itself with, for example, inputs from relevant midline structures that detect errors or response conflict ((Dehaene et al., 1994) (Botvinick et al., 2001)). Alternatively, if these other structures perform the monitoring function themselves, then the right prefrontal cortex's role would be to modulate arousal levels based on their outputs. Either way, it would seem to be the case that vigilant attention operates in an interactive way with other executive functions, a topic that we will turn to next. Relationship between vigilant attention and other executive systems We conceive of the right parietal-prefrontal network and its interactions with the midbrain arousal systems as the circuitry by which vigilant attention is maintained. This circuitry can be “turned up” endogenously or with exogenous support. Within this system, we believe that the prefrontal cortex plays a central role in maintaining and monitoring optimal arousal levels to match current task demands. Although we can conceive of this system as somewhat independent and autonomous, in order to be responsive to changing tasks demands, changing performance levels, or changing physiological resources such as might be depleted by fatigue, monitoring processes must be tightly coupled with, or intrinsic to, its functioning. In addition, this system works in the service of current task goals and close interaction between it and goal representations are to be expected. Consequently, the type of attentional control that has been the focus of this chapter need 17 Robertson and Garavan 18 not be isolated from the other aspects of attention linked to selection, working memory and switching that were mentioned at the beginning of this chapter. The nature of the relationship between goal state representation and vigilance is, however, not very well understood. It may be the case that the goal state (e.g., take the train safely from station A to station B) may call upon the vigilant attention system to ensure the goal is attained in the circumstances already described in which exogenous support is minimal. However, if the goal can be actively maintained in a focus of attention within working memory (Garavan, 1998) then this may, in fact, reduce reliance on the vigilance system. For example, inhibiting a response to the number 3 in the SART task is quite easy if you have just refreshed that rule, perhaps by subvocally re-iterating to yourself that you must not respond to 3's (indeed, we have demonstrated in patients with impaired fronto-parietal function that precisely this type of verbal regulation can compensate for sub-optimal vigilance (Robertson et al., 1995). Inhibiting to the 3 becomes difficult - and reliant on the vigilant attention system - if the "inhibit to 3" goal is no longer prominent but, instead, has been allowed to decay. A number of lines of evidence implicate left prefrontal areas in this type of goal maintenance (Brass and Cramon, 2002; Frith and Dolan, 1996; Garavan, 1998; MacDonald et al., 2000; Ruchsow et al., 2002) which implies inter- hemispheric interaction between goal representations and vigilant attention. Combined, this conceptualisation of vigilant attention and its interaction with goal representations provides a basis for different types of attentional impairment. First, the subcortical arousal or cortical vigilant attention systems - the "machinery" of attention - might be damaged leading to gross vigilance impairments that may not be easily amenable to rehabilitation. Second, the functioning of the task goal system and/or its 18 Robertson and Garavan 19 interaction with the vigilance systems may be compromised. That is, while the machinery (i.e., the ability to attend) may be intact, the mechanisms by which this machinery is mustered in the service of task goals might be compromised. Patients who can muster sufficient attentional resources with exogenous support (e.g., cueing, phasic alerting) but have difficulty doing so without this support may have this second type of dysfunction. We can perhaps gain an insight into the interactions between vigilant attention and other executive functions by observing the processes involved in preparing for an attentionally demanding task. A predictive cue that warns of an impending task involves the endogenous activation of a vigilant state. We have recently shown that the areas activated in anticipation of a response inhibition include right prefrontal and parietal cortex (Hester et al., under review). This may reflect either engagement of the vigilant attention system or, given that these areas were necessary for the subsequent inhibition, may reflect preparatory activation of task-specific areas. Left prefrontal cortex was also activated following the cue which we believe reflects task set re-activation as described above. Furthermore, what uniquely distinguished a successful preparation from an unsuccessful one (i.e., despite the cue, a commission error was made) was the deactivation of midline prefrontal areas that are thought to be involved in the monitoring of internal emotional states (Gusnard et al., 2001). The deactivation of task inappropriate areas confirms a finding of similar deactivations underlying good performance in a Rapid Visual Information Processing task (Lawrence et al., in press). Together, these additional processes, the preparatory activation of task relevant areas and deactivation of task 19 Robertson and Garavan 20 inappropriate areas, may serve as additional attentional mechanisms that obviate reliance on the vigilant attentional system. The notion that vigilant attention is linked to deactivation of inappropriate areas raises the question as to whether inhibition can be regarded as one means by which vigilant attention is maintained: in the case of the London train driver, for instance, the ability to detect the yellow warning signals may have been predicated on the ability to inhibit non task-relevant cognitions, emotions and perceptions. While not synonymous, vigilant attention and inhibition may be strongly overlapping functions both functionally and anatomically, which would explain the very strong similarity in activation patterns for vigilant attention and inhibitory tasks. Figure 3 shows activation associated with GO/NOGO response inhibition based on a meta-analysis of 58 subjects (Garavan and Hester, in preparation). Robust event-related activation in the right dorsolateral prefrontal and right inferior parietal lobule parallels tonic activation patterns observed for vigilance tasks. The speculation follows that vigilant attention might be conceptualised as a continuous inhibition of task irrelevances. Also shown on the figure is a more ventral activation on the right inferior frontal gyrus. Inhibition-related activation in this inferior region was significantly greater in those subjects scoring higher on the cognitive failures questionnaire that we described above as correlating with SART performance. The region in question in figure three also shows a correlation between inhibition-related activation and age, suggesting that this structure is used more both by highly absentminded and older people (Garavan and Hester, in preparation). Furthermore, older subjects also showed significantly greater left prefrontal activation than younger subjects, consistent with an age-related increased dependence on the left hemisphere task-set re-activation 20 Robertson and Garavan 21 mechanism. While the relationship between vigilant attention and inhibition must be investigated further, these results offer encouragement in the search for the neuroanatomical bases for these executive functions and their relationship to normal individual variability and pathological disturbance. Figure 3 about here Attention Deficit Hyperactivity Disorder Attention Deficit Hyperactivity Disorder is a complex condition with a number of different subtypes, and a range of associated cognitive and motivational impairments (Castellanos and Tannock, 2002). What is interesting about this disorder in the context of the current chapter is the fact that the Inattentive subtype of the disorder includes a profile of impaired sustained attention, absent-mindedness, distractibility and action slips that are extremely close to the pattern of adult behaviour we have described in this chapter as being linked to a deficient vigilant attention system. Bearing in mind this similarity in behaviour patterns, and without wishing to ignore the abnormalities in other brain regions such as the caudate nucleus and the vermis of the cerebellum that have been identified in ADHD, it is of considerable interest that there are also abnormalities in the right frontal lobe – particularly in the underlying white matter (Castellanos et al., 1996) – in ADHD. Furthermore, we have also shown that, compared to IQ-matched controls, children with ADHD are impaired on sustained but not selective attention performance (Manly et al., 2001). The remarkable responsiveness of these attentional deficits in ADHD to methylphenidate or amphetamine (Solanto et al., 2001) – drugs that potentiate noradrenergic as well as dopaminergic release – also links the vigilant attention system and its arousal-modulating 21 Robertson and Garavan 22 role to this clinical syndrome. This is particularly true given the EEG evidence of low tonic arousal as manifested by high theta power in the EEG spectrum (Bresnahan and Barry, 2002). We have recently shown that the fixed sequence SART that discriminated traumatic brain injured patients from controls so well, also discriminates between ADHD and controls (Connell et al., in preparation). Furthermore, tests of vigilant attention in a children?s battery of attention consistently discriminate ADHD participants from controls in a way that selective attention tests do not (Manly et al., 2001). To summarise, important aspects of the ADHD syndrome may constitute an important manifestation of deficits of the vigilant attention system, and therefore progress that has been made towards rehabilitation deficits in this system may potentially be applicable to ADHD: it is to this final question that we turn now. Rehabilitation and Vigilant Attention The ability to sustain vigilant attention seems to be an important factor in determining recovery of motor and other function following stroke (Ben-Yishay et al., 1968; Blanc- Garin, 1994). Furthermore we have shown that motor recovery following stroke over a 2-year period was significantly predicted by measures of sustained attention taken 2 months after right hemisphere stroke. Specifically, the ability to sustain attention to a tone counting task (a validated measure of sustained attention related to right frontal function (Wilkins et al., 1987)) at two months post-stroke predicted not only everyday life function 2 years later, but also the functional dexterity of the left hand in a pegboard task (Robertson et al., 1997b). Impairment in sustained attention may also be a key factor in the development of the disabling condition unilateral spatial neglect – a relatively common consequence of right 22 Robertson and Garavan 23 hemisphere stroke (Husain and Rorden, 2003; Robertson, 2001). Apart from the disabling consequences of impaired vigilant attention itself, it is likely that impairments in this system have more wide-ranging consequences for recovery from brain damage and the learning that underpins rehabilitation effects (Robertson and Murre, 1999). It is possible to enhance vigilant attention both in the short term through exogenous means (Manly et al., 2002; Manly et al., in press-a) and also over longer periods by training patients endogenously to implement metacognitive, verbally-regulated strategies (Robertson et al., 1995). We have further shown that short-term exogenous activation of the vigilant attention and arousal systems can temporarily alleviate neglect-induced spatial bias (Robertson et al., 1998). Similar methods have now been incorporated as an element in a more comprehensive and successful system of rehabilitation for executive problems following frontal lobe damage (Levine et al., 2000). Conclusions When you have driven your train a hundred times through a light that was always green, stit is all too easy for the brain to miss the yellow light that appears on the 101 journey - and to let the train-driving motor programme run on, unsupervised - occasionally to catastrophe. If that yellow light is detected, the accelerator handle released, and the train slowed down in preparation to stop at the next light, it is thanks to the right hemisphere of the brain, and in particular the right dorsolateral prefrontal and inferior parietal cortices – working in concert with thalamic and mesencephalic circuits. Repeated, unchallenging stimuli in the context of highly practiced actions diminish arousal, dull sensory responsiveness and blunt vigilant oversight of one?s actions and environment. The reciprocal action of a right hemisphere cortical network on the one hand, and a 23 Robertson and Garavan 24 subcortical arousal network on the other, has evolved to protect against such a potentially dangerous diminution of awareness and monitoring. Because so much of what we do is practised and automatic, this system is needed throughout our waking day. 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Figure 2a Proportional ommission errors increase as no-go target probability decreases (SART) (Manly et al., 1999) 28 Robertson and Garavan 29 Figure 2b Commission errors on 11% no-go versus 50% no-go (SART) for high and low cognitive failure-prone subjects (Manly et al., 1999). Figure 3 Extensive dorsolateral and parietal activation in red is shown for event-related response inhibition. Activation in blue on the right inferior frontal gyrus was correlated with the CFQ score suggesting a greater reliance on this right prefrontal area in those subjects scoring highest on everyday absentmindedness (Garavan and Hester, in preparation). 29 Robertson and Garavan 30 12 10 8 Random SART6 Fixed SART4 2 0Control errorsTBI Errors 30 Robertson and Garavan 31 9 8 7 6 5High CFQ4Low CFQ3 2 1 011% lure50% lure 31 Robertson and Garavan 32 18 16 14 12 10 Proportional error8 6 4 2 011% Lure22% lure50% lure 32 Robertson and Garavan 33 33 Robertson and Garavan