(a) Evolution of the question and initial response
Their relatively large size, late evolutionary development and rich anatomical connectivity all strongly suggest a central role, or roles, for the frontal lobes in human cognition and emotion. That there are so many competing theories about frontal functions despite the many recent advances in lesion and imaging research illuminates the difficulty in understanding this complex region.
The difficulties in studying the frontal lobes are myriad. First, there is no particular predisposition for a neurological disorder to the frontal lobes. Although cerebrovascular disorders may damage only the frontal lobes, the number of individuals with focal frontal pathology is not particularly high. The pressures of publication, the time required to collect an adequate sample of focal frontal lobe lesions and the rapid change in theoretical positions during the period of data accumulation often predispose researchers to use more convenient samples (e.g. undifferentiated traumatic brain injury) as a proxy. Such studies have practical value for understanding the target population, but precise brain–behaviour relationships cannot be determined. Central roles for various frontal regions have been proposed for both cognitive and emotional functions, and both may be recruited for complex tasks—gambling decision, investment planning, etc. Lesions may disrupt either or both, depending on site. It may be the interaction of emotional status and cognition that determines many behaviours, but it is the cognitive aspect of tasks that are defined by executive functions.
Many prominent theoretical positions emphasized the dominant role of the frontal lobes in organizing cognition, thus such terms as supervisory system
and central executive
. A controversy within this approach has been related to the unity (Duncan & Miller 2002
) versus diversity (Stuss & Benson 1986
; Shallice 2002
) of executive functions. In the early 1990s, we embarked on a research plan to examine whether such an executive system could be fractionated (Stuss et al. 1995
). Our approach was different from that often used in neuropsychological research. Instead of selecting one test or one process that was considered executive, we took a ‘root and branches’ approach. We selected attention (the ‘root’) as the cognitive focus owing to its prominent role in many influential theories of frontal functions (e.g. Heilman & Watson 1977
; Shallice 1982
; Mesulam 1985
; Norman & Shallice 1986
; Posner & Petersen 1990
; Knight 1991
; Paus et al. 1997
; Godefroy et al. 1999
; Sturm & Willmes 2001
). We elected to study patients with focal lesions to demonstrate that a region was essential for an attentional process, as opposed to simply being activated during a process (as, say, with functional magnetic resonance imaging, fMRI). All published studies addressing attentional deficits in patients with single focal frontal lesions were reviewed. The tasks used in the various studies could be grouped into a relatively small number of categories. Based on our review of the different papers, we proposed a limited number of distinct frontal lobe processes (the ‘branches’) which could explain the performance of each task. The reviewed papers also implied potential frontal localization of at least some of these processes. This initial review implied that there was no common central organizing role of the frontal lobes; rather, there were independent control processes related to different brain regions. We concluded that
If we are correct that there is no central executive, neither can there be a dysexecutive syndrome. The frontal lobes (in anatomical terms) or the supervisory system (in cognitive terms) do not function (in physiological terms) as a simple (inexplicable) homunculus. Monitoring, energizing, inhibition, etc.—these are processes that exist at many levels of the brain, including those more posterior ‘automatic’ processes. Owing to their extensive reciprocal connections with virtually all other brain regions, the frontal lobes may be unique in the quality of the processes that have evolved, and perhaps in the level of processing which might be labelled ‘executive’ or ‘supervisory’.
Bolstered by this review and using Norman & Shallice's (1986)
supervisory system as our launching point, we undertook a programme of research to examine whether we could differentiate and define frontal processes within a supervisory system. Such processes had to be domain-general, in that they would be necessary for different cognitive modalities (e.g. language, memory) as well as basic attentional tasks such as reaction time (RT). Domain-general implies that different tasks in one modality or similar tasks in different modalities would show similar effects of specific lesions. Finally, the results had to be replicable across different groups of frontal lobe patients to ensure there was no particular subject group bias. Other researchers have embarked on a similar journey (e.g. Shallice & Burgess 1991
; Burgess & Shallice 1994
; Godefroy et al. 1994
; Diaz et al. 1996
; Robbins 1996
; Burgess et al. 2007
). This paper will necessarily focus on our own programme of research, but results from other laboratories will be presented where appropriate.
(b) Methodological philosophy
We began with three assumptions of what would be necessary for success. First, the history of research on ‘executive’ functions has conflated psychological theories with anatomical ones, so we focused our investigation on the effects of frontal injuries, not on an investigation of executive functions (which can be examined independently of any brain relationship). This required including only patients with purely focal frontal single lesions. Second, restricting the patients to those with vascular aetiology would profoundly limit the regional representation of frontal lesions, so patients with different aetiologies were accepted if they met specific conditions (see Stuss et al. 1995
for a review of these conditions). In addition, we and others have demonstrated several times that, under these conditions, the location is more important than the aetiology (Elsass & Hartelius 1985
; Burgess & Shallice 1996
; Stuss et al. 2005
; Picton et al. 2006
, in press
). Third, in order not to confound acute diffuse problems with more focal impairments, we tested patients in the chronic stage of recovery, ideally after three months. As patients' lesions become more and more chronic, it is possible that brain–behaviour relationships are affected by brain plasticity and reorganization. The evolution of these relationships from acute to post-acute to chronic phases is probably interesting, but would require another programme of research following patients during the course of recovery, supported by imaging. Recent data do suggest that similar patterns of behaviour may be observable in both acute and chronic patients (Stuss et al. 1994
; Alexander et al. 2003
; Turner et al. in press
A process must be isolated to demonstrate a specific brain–behaviour relationship. Process dissociation was used for the standard clinical tests where possible. In the experimental tests, the goal was to devise simple tests that probed single processes and then manipulate difficulty and context to probe more complex processes.
The next step was to devise a method to assign frontal lesions to specific frontal regions to determine whether there were any regional effects on each process. There are several different methods to achieve this (Stuss et al. 2002a
). In this paper, we present data from two approaches. In some studies, the frontal patients are compared based on a coarse predominant location of the lesion: left lateral (LL); right lateral (RL); inferior medial (IM); and superior medial (SM). In addition, however, we were able to focus on much more precise architectonic regions with a ‘hotspotting’ method developed by us (Stuss et al. 2002a
). The lesion for each patient is mapped onto the Petrides & Pandya (1994)
architectonic template. For every patient, each architectonic region is identified as significantly damaged or not. Then, for the measurement in question, the performance of individuals who have damage in a particular region is compared with all those who do not have damage in that region. This hotspotting approach is open to criticism of too many comparisons and the risk of type I error. We have been cognizant of this problem, but given the substantial difficulties of lesion-based research and the potential benefits of identifying specific brain–behaviour relationships, this approach seemed reasonable, at least as a first approximation of focal effects. Furthermore, if the results can be replicated across different tests that demand a similar process, and across different patient groups, the summated evidence for that brain–behaviour relationship is strengthened. At the very least, having these findings in lesion research provides a plausible approach for verification in other studies, or for devising a more specific region of interest hypothesis.
Lesion research demonstrates that some structure within the lesion is critical for impairing a task. Comparing patients with similar, partly overlapping lesions allows increasingly fine identification of which structures are essential. Lesion studies are not equivalent to functional imaging studies that demonstrate activation of a region during defined tasks. The activation may or may not represent a critical role in the performance of the task. Nevertheless, there is considerable convergence of the neuroimaging and lesion studies.
(c) The basic paradigms
If executive functions are truly ‘superordinate’ and ‘domain-general’, it should be possible to determine their effects across a variety of tasks. Four different sets of data are used in support of our hypothesis of process fractionation within the frontal lobes. We used classic ‘frontal’ tasks (Wisconsin Card Sorting Test, WCST, Milner 1963
; the Stroop test of interference, Stroop 1935
; Comalli et al. 1962
), other tasks with a control requirement but in different modalities (language—verbal fluency, Borkowski et al. 1967
; memory—list learning, Delis et al. 1987
), feature integration test (FIT; Stuss et al. 1989
) in which complexity of response distractions could be manipulated, and finally, a novel battery of tests (ROBBIA, ROtman-Baycrest Battery to Investigate Attention; Stuss et al. 2005
), that systematically probe levels of attention and response control (all of the tests are shown and explained in and appendix A
). In each section below, we start with the more precisely defined ROBBIA tests, ending with the more complex clinical tests.
Figure 1 The paradigms used in the various studies. (a) Based on commonly used neuropsychological tests of ‘frontal lobe’ functions: adapted from Wisconsin Card Sorting Test (WCST) and Stroop. (b) Language and memory tests that require executive (more ...)
(d) Summary of approach
Our goal was to determine whether all focal frontal lesions produced a similar impairment in cognitive supervisory control or whether lesions in different regions produced specific impairments that might or might not appear on a task depending upon the particular demands of the task.1
There is currently evidence for at least three separate frontal processes related to attention, each related to a different region within the frontal lobes as illuminated by deficit profiles after injury. We have labelled these processes as energization
, task setting
. For each process, we start with our conclusions, and present a current description of the process and data that support the existence of each distinct process. In some instances, we have reanalysed the original data to be consistent across the tasks. The possibility of a type I error is minimized by the replication of the findings: the replications often occur across the tasks, including tasks of different cognitive modalities (e.g. RT paradigms, memory); the same results can be demonstrated with different patient groups, minimizing the possibility that the results are unique to a specific set of patients2
; in some cases, there is supporting evidence from other research laboratories.
(e) Definition of ‘energization’
Energization is the process of initiation and sustaining of any response. The basis for proposing an energization function comes from neurophysiological observations that there is an internal tendency for any neural activity to become quiescent in the absence of input. A natural extension of the supervisory system model is to assume that, in the absence of external triggers or motivational conditions to optimize responding, lower level perceptual or motor schemata would have to be energized or re-energized when activation becomes low, as would be required, for example, for detecting occasional stimuli or performing occasional motor acts. Without energization, setting and sustaining a specific selected response cannot occur and maintaining performance over prolonged periods of time will waver.
(f) Evidence for energization and putative frontal localization
Deficient energization is most consistently associated with lesions in the SM region bilaterally, with some evidence for a more important role for the right SM area ().
Figure 2 Quantitative data illustrated in graphs for coarse frontal anatomical groupings (most often, left lateral (LL), right lateral (RL), inferior medial (IM) and superior medial (SM)) compared with a matched control (CTL) group (see Stuss et al. 1998, for (more ...)
The ROBBIA simple
and choice RT
tests differed in that the choice RT tasks required an easy differentiation of the feature of the target stimulus and the presence of distractors (Stuss et al. 2005
; see and appendix A
for further task details). In both the tests, there was a significant slowing of the SM patients only, with the hotspotting technique highlighting primarily areas 24 and 32 (a
). The involvement of the SM region appeared to be more pronounced in the somewhat more demanding task. In the simple RT, the SM group was marginally slower than the control group (p
=0.06); in the choice RT, the significant difference was p
=0.007. The slowing was not a factor of lesion size, since the SM group was the slowest by far, and there was no relation of lesion size to RT in the SM group (e.g. p
=0.6–0.9 for the different tasks). Lesion location is a better predictor of response slowing than lesion size. The RT results of the feature integration test
(Stuss et al. 2002b
), similar in design to the simple and choice RT tests of ROBBIA, yielded similar results (b
In the prepare RT
test (Stuss et al. 2005
), we analysed whether a warning stimulus presented either 1 or 3
s prior to a choice RT affected speed of response. In all the three conditions (no warning, 1
s warning and 3
s warning), the overall significant SM slowing remained. All groups benefited from the 1
s warning, and all groups were slower on the 3
s warning condition compared with the 1
s warning. The 3
s warning RT was still faster than without a warning in all but one group, the SM group. c
shows the difference in RT between the 3 and 1
s warning conditions. The loss of benefit for the SM group from the longer warning interval is compatible with a deficit in sustaining energized attention and response systems. The fact that there were not significant differences in errors among the conditions suggests that this cannot be secondary to a deficit in noticing and reacting to signals.
The ROBBIA concentrate
test perhaps illustrates the energization deficit most clearly (Alexander et al. 2005
). It is very simple in structure but requires high levels of sustained attention. Only patients with lesions in SM frontal regions had significant RT slowness, and this was consistent across the entire test. This group's mean RT was 33% greater than the other patient groups and the control subjects. The prolonged RT was not simply due to fatigue or errors, as the slowness was evident from the beginning across 500 trials. We had initially hypothesized that the anterior cingulate gyrus (ACG) would be the critical region (Paus et al. 1997
; Luu et al. 2000a
). However, the critical region was larger and involved supplementary motor area (SMA) and the preSMA region (P & P areas 24, 32, 9 and 46d). The noted slowness with right SM lesions on this test requiring sustained concentration was interpreted as an insufficient energizing of attention to respond.
The ROBBIA tap
test consisted of two simple timing tasks, one requiring tapping to an externally driven stimulus (every 1.5
s), and another demanding maintenance of the same regular response rhythm without any external stimulus (Picton et al. 2006
). Normal performance is illustrated in the control group (see CTL in e
). An increase in the variability of timing performance, as the task continued
(see rising arrow), was noted in patients with lesions to the SM regions of the frontal lobe (e
). The SM frontal area is necessary to maintain consistent timing performance over prolonged periods of time.
This energization function was also revealed in two standard clinical frontal lobe tests. An energization function should be applicable to any task. Evidence for this function was observed in a verbal fluency
language task, requiring the generation of words beginning with a specific letter over 60
s (Stuss et al. 1998
). All groups produced fewer words over time, but the total of the last 45
s (grey versus black bars in f
) was greater in all but the SM group. The critical region again was the SM area (f
We administered the classic Comalli et al. (1962) Stroop
version with three conditions: word reading; colour naming of colour patches; and colour naming of colour words printed in a colour different from that of the word (interference; Stuss et al. 2001
). Patients with frontal and non-frontal pathology were compared with normal control subjects. Patients with posterior lesions were not significantly deficient in any condition. Within the frontal patients, bilateral SM frontal as well as right superior posteromedial lesions were significantly associated with increased errors and slowness in response time for the incongruent condition (g
), an impairment interpreted as failure of maintenance of consistent activation of the intended response in the incongruent Stroop condition. This inability to maintain an activated response mode appeared consistent with the rapid decline in preparatory activation from 1 to 3
s after a warning stimulus in the prepare RT.
(g) Interim summary for energization
Decreased facilitation (energizing) of the neural systems that are needed to make the decisions (contention scheduling) and initiate the responses (schemata) is impaired after bilateral SM frontal lesions, with suggestion of greater importance for the right SM region. Supportive data came from different RT tasks, from studies in different modalities (RT, language) and across different patients. The SM deficit was demonstrated by prolonged simple RT, proportionately greater prolongation of choice RT, inability to sustain preparation to respond, inability to maintain consistent short time-intervals in a task, diminished output in a verbal fluency test, and increased errors and slower speed in a Stroop test. The localization is similar in each study, although comparison of the different tests suggests that there was some relationship of the severity of the deficit with the demands of the test. The time course across the tasks (e.g. from a few seconds—prepare RT to 1
min—fluency) implies that this region is important for initial energization as well as sustaining of energization; future research might also unveil potential localization or context differences related to the initial energization versus sustaining.
These findings are also concordant with clinical observations. Bilateral damage to ACG and SMA produces akinetic mutism, a dramatic example of deficient energizing (Plum & Posner 1980
; Devinsky et al. 1995
; Alexander 2001
). Changes in activity of the cingulate cortex occur as a function of sleep stages (Hofle et al. 1997
), vigilance (Paus et al. 1997
) and alertness (Luu et al. 2000a
). We consider the energizing deficit in SM patients independent of general arousal as, in our studies, there was no correlation or interaction of slowness and reported sleepiness or level of motivation among groups (Stuss et al. 2005
). We therefore think that energizing schemata is the process that allows subjects to maintain their concentration on a particular task. In the neurological literature, this would correspond to phasic attention (Stuss & Benson 1984
); in the information processing literature, energization would correspond to the effort system of Hockey (1993)
(h) Definition of task setting
Each of the tests in which the task setting attentional process is demonstrated requires the ability to set a stimulus–response relationship. Task setting would be necessary in the initial stages of learning to drive a car or planning a wedding. This may be initiated a priori and is most often learned and consolidated through trial and error. In easier tasks, task setting would be more relevant in the early stages. Any deficit would be more evident under conditions that require continuous refreshing and suppression of more salient responses. The establishment of the connection between a stimulus and a response would require formation of a criterion to respond to a defined target with specific attributes, organization of the schemata necessary to complete a particular task and adjustment of contention scheduling, so that the automatic processes of moving through the steps of a task can work more smoothly. Owing to the role of the SM region in energization in some tasks addressing task setting (and monitoring below), there could be evidence of SM involvement. This is not illustrated.
(i) Evidence for the task setting process and putative frontal localization
Task setting is consistently impaired after damage to the LL region of the frontal lobes, most often with a more ventrolateral distribution ().
Figure 3 ‘Task setting’ process consistently impaired after damage to the LL frontal region. is organized in a similar manner to . The tests are illustrated and explained in and appendix A. There were no significant impairments (more ...)
Errors in the ROBBIA concentrate (see for task description) task were noted primarily in the first 100 out of 500 trials, and these were made maximally by patients with damage to left frontal P & P Areas 44, 45A and 45B and 47/12 (Alexander et al. 2005
). This was not associated with decreased RT (no time–accuracy trade-off) or increased RT (no awareness and monitoring of errors). The difficulty was interpreted as defective setting of specific stimulus–response contingencies (see also Godefroy et al. 1994
). Once in ‘task responding set’ (after the first 100 trials), there were no deficits in any subgroup of patients.
task in ROBBIA was a variant of the Stroop, a test which assesses the ability of patients to control intact cognitive operations under the condition of conflicting possible responses (Alexander et al. in press
). Lesions of the left ventrolateral region (areas 44 and 45) produced an impairment in setting contingent response rules as indexed by the number of false alarms (b
The importance of isolating the process is illustrated by an analysis of the feature integration test complex condition
(three features). We had hypothesized that making false positive errors would be an index of task (criterion) setting to respond appropriately to the target as opposed to non-targets (Stuss et al. 2002b
). The first architectonic analysis was surprising—the RL region appeared to be most associated with this type of error (cf. c
). However, patients with damage to this RL region made errors of all kinds, which we interpreted as a monitoring impairment (see below for analysis of just false negative errors). We subtracted the false negative from the false positive responses to isolate the patients who made primarily the type of errors indicating that they could not set a task criterion to respond ‘yes’ (response bias—false positives). When the architectonic analysis was redone isolating the false positive responders, the major area of impairment was now focally left frontal (c
Figure 4 ‘Monitoring’ process consistently impaired after damage to the RL frontal area. The tests are illustrated and explained in and appendix A. The dependent measures vary among tasks. The RTs for the short (3, 4s) and long (more ...)
Another important example of process isolation, and the need to understand that the experimental manipulation may define what a specific measure may represent, occurred in the analysis of the WCST
results (Stuss et al. 2000
). In the 128 card condition, set loss would probably reflect primarily the potential trial and error learning of the correct sorting criterion, in a way similar to the early trial errors in concentrate, as well as some degree of monitoring. In the 64B condition, in which the subject had been informed of the three sorting criteria, what criterion to start with and when the criterion had changed (i.e. the task parameters had been quite specifically established), set loss errors more probably indexed the online monitoring and checking of performance, since the task had been set by the explicit instructions. The hotspot analysis confirmed this hypothesis. In the 128 condition, although set loss problems were apparent after both LL and RL damage, the identified most relevant area was the LL region (areas 9/46v, 45A; d
); in 64B, set loss was related to damage in the RL region (areas 6B, 44, 45A and 45B; d
Task setting impairment, as indexed by difficulty in establishing an appropriate response criterion, can also be observed in memory
tasks. We have now administered three different word lists (one of them being the standardized California Verbal Learning Test, CVLT) to three different groups of frontal lobe patients. In the first study, the left frontal group was most impaired in the number of false positives (the hotspotting technique had not yet been developed; Stuss et al. 1994
). The number of false positives in the CVLT study was associated with damage in the LL area 45A (Alexander et al. 2003
One task resulted in a more caudal localization than the other task setting effects. In a response inhibition (NOGO
) task, four equiprobable stimuli (letters A, B, C and D) were presented in two different conditions (Picton et al. in press
). In the first condition, the subject responded to the letter A only; in the second condition, the subject responded to the letters B, C and D, and not to A. These two conditions were called the ‘improbable-go’ and the ‘improbable-nogo’. An increased number of false alarms (incorrect responses to the nogo stimulus) were found primarily in patients with lesions to left SM (6A) and LL regions' area (8B, area 9/46) of the frontal lobes (f
). Although our patients were primarily right handed, the involvement of the LL and superior region in nogo motor control is probably independent of response hand (Talati & Hirsch 2005
). Our localization results appear comparable to the original nogo study of Drewe (1975a
), clinical studies (Verfaille & Heilman 1987
) and other human and animal research (Brutkowski 1965
; Iversen & Mishkin 1970
). Some of the variability of the results in other go–nogo paradigms may derive from the differing cognitive requirements.
(j) Interim summary of task setting
If the task setting process can be isolated, there is consistent evidence that left frontal damage disturbs this process. The task setting–left frontal relationship was observed in different RT tests, the clinical WCST and word list learning. Different patient populations were examined in several of these studies. It is yet uncertain if any variation in task setting localization observed in our tasks is a reflection of inadequate sampling of different brain regions or a reflection of a more general left frontal function interacting with more specific task demands (e.g. response task setting). In general, our findings support Luria's (1966)
postulate that damage to the left frontal lobes damages the patient's ability to use task instructions to direct behaviour (verbal regulation of behaviour), even when clearly able to comprehend their meaning.
Other lesion studies using similar patients attempted to identify regional frontal effects using the Stroop task and define underlying impaired neural mechanisms; with some discrepancies in localization details attributable to differences in patient populations and precision of lesion definition, they, in general, support our findings that LL lesions affect setting of stimulus–response contingencies (while SM lesions affect energizing attention to task; Perret 1974
; Richer et al. 1993
We believe that fMRI studies using variations of the standard Stroop paradigm also generally support our hypotheses. Derfus et al. (2005)
completed a meta-analysis of all neuroimaging studies with sufficient data on task switching and the Stroop published from 2000 to 2004. The major localizations for the Stroop studies were in the left inferior frontal gyrus (IFG) (areas 44 and 6; with the next largest clusters in bilateral SM cortex, areas 32/6 and 32/9; see also Brass & von Cramon 2004
). Localizations were similar if tasks had similar properties to the Stroop. Their conclusion was that the left VL region was the critical region for updating task representations.
(k) Definition of monitoring
Monitoring is the process of checking the task over time for ‘quality control’ and the adjustment of behaviour. Monitoring may occur at many levels: the ongoing activity in a task-specific schema; the timing of activity; anticipation of a stimulus actually occurring; detecting the occurrence of errors; and detecting discrepancies between the behavioural response and external reality. If an anomaly or problem is detected by monitoring, then an interrupt or explicit modulation of the ongoing programme would occur.
(l) Evidence for the monitoring process and putative frontal localization
Our results demonstrate that lesions of the RL prefrontal cortex critically impair monitoring as defined previously ().
Interstimulus intervals (ISI) in the ROBBIA simple and choice RT tests provided the opportunity to assess the ability of the different patient groups to monitor the interval between trials. The control group showed a normal foreperiod effect, namely a gradual decrease in RT with ISI (Niemi & Näätänen 1981
). Only the RL group exhibited a reverse foreperiod effect, an increase in RT with increasing ISI as opposed to the decrease in the control group and all other patient groups (a
). This was evident across both tests, although more evident in the more demanding choice RT test. The architectonic hotspotting of the difference in RT between late and short ISI revealed maximum impairment in areas 9, 9/46d and 9/46v. Vallesi et al. (in press)
, using TMS over right frontal lateral, left frontal lateral and right angular gyrus in healthy young adults, demonstrated an abnormal foreperiod effect independent of any sequential effect only after RL stimulation. Damage to the RL frontal region impairs the modulation of expectancy. Our study had suggested that this was related to time estimation, but Vallesi used much shorter ISIs (0.5–1.5
s) and revealed the same effect, indicating that the role of RL region in monitoring is not just over longer periods of time. The RL region may be involved in monitoring of temporal information which may be required explicitly as in time reproduction or discrimination tasks (e.g. Basso et al. 2003
; Lewis & Miall 2003
; Picton et al. in press
) or implicitly as in the foreperiod effect.
In the tap experiment (Picton et al. in press
), requiring tapping at a rate of once in every 1.5
s either in response to an external stimulus or self-timed, patients with lesions to the RL frontal lobe, particularly involving P & P area 45 and the subjacent regions of the basal ganglia, had an abnormally high intra-individual variability in both self- and tone-timed conditions (b
). This impairment was interpreted as deficient monitoring of the passage of the intervals, although a potential role in generating time-intervals could not be excluded.
The monitoring deficit in relation to checking performance of errors was noted in the FIT (Stuss et al. 2002b
). In contrast to the LL group who exhibited false positive errors in the complex three-feature integration condition, the RL group made errors of all kinds: false positives; false negatives; and omissions. Architectonic localization of the false negative errors alone, to minimize any task setting impact, reveals the importance of the RL region in monitoring performance (c
Our modification of the WCST, moving from less (128 card) to more structure (64B condition), revealed that set loss errors were more associated with the LL frontal region, when the task was unstructured and subjects were learning what the criteria were and how to perform the task. But the same measure was associated with the RL region instead when the major task demands have been explained to the patients (informed of the three criteria that colour would be the first and the criterion would change after 10 consecutive correct trials), interpreted as deficient monitoring and checking of performance over time (d).
In our original study of word list learning
, there was an association of RL pathology with two measures that we considered monitoring (Stuss et al. 1994
). Double recalls were defined as the recall of a word that had already been recalled, but only after at least one intervening word. Inconsistency was a measure of the ‘in and out’ recall of the same word over different trials. In the replication of this study with the CVLT (Alexander et al. 2003
), the hotspotting technique did support the predominantly RL (primarily ventrolateral) relationship with the measure of inconsistency. A more direct reflection of this ‘checking’ role of the RL region was achieved by Turner et al. (in press)
. Functional imaging of memory also indicates an RL role in monitoring of memory (Henson et al. 1999
; Fletcher & Henson 2001
(m) Interim summary of monitoring
Lesions of the RL frontal region produce impairments in monitoring and checking of performance over time. This has been shown by a failure to show a decrease in RT with variable foreperiods, contrasted to normally maintained energizing over a fixed warning interval. In essence, the patients fail to note that a stimulus has not yet occurred, hampering their preparedness to respond. The RL group also fail to note that an error has occurred and do not adjust their performance accordingly. These data and interpretation are compatible with imaging and lesion research in ‘vigilance’ and monitoring (Wilkins et al. 1987
; Pardo et al. 1991
; Rueckert & Grafman 1996
; Coull et al. 1998
; Henson et al. 1999
; Fletcher & Henson 2001
; Shallice 2001
). Functional lesions using transcranial magnetic stimulation over short ISIs suggest that the monitoring is not necessarily limited to ‘vigilance’ over time in the classic sense (Vallesi et al. in press
The difficulty in monitoring the ongoing passage of the ISI to prepare responsiveness over time is corroborated by the results of the TAP experiment. Although it is possible that prefrontal lesions impair time perception (e.g. Mangels et al. 1998
), the variability in time perception throughout the entire experiment whether paced or unpaced promotes the idea of a deficit in monitoring a ‘clock’.
Comparing the SM and RL groups illuminates the type of regionally specific effects that we originally proposed. The RL group alone revealed an abnormal foreperiod effect (ISI effect) when ISI was manipulated. In the TAP test, the patients with RL pathology showed greater variability of performance throughout the test; the SM patients, on the other hand, showed a significant increase in the variability of the responses as the test continued. Taken together, one might hypothesize that the areas of the RL region may interact with the SM regions to initiate or maintain phasic arousal. The RL frontal lobe is crucially involved in the ongoing control of timed behaviour, either owing to its role in generating time-intervals or in monitoring the passage of these intervals. In contrast, the SM regions of the frontal lobe are necessary to maintain consistent timing performance over prolonged periods of time. Lesions to either of these areas may thus generally slow the responses, but for entirely different reasons that become clear only when the fundamental processes dependent on the different regions are explicitly measured.