Cognitive neuroscience and neuropsychology have emphasized the link between anatomical structures to specific functions in an attempt to understand complex human functions. Although this has been useful for basic functions (eg, visual and motor functions), this approach has less utility for understanding higher order functions. Complex higher order functions considered characteristic of humans are challenging to localize.1 These functions contribute to our ability to reason, plan, problem solve, meet goals, and behave appropriately in a specific situation (for review, see references 2–4). Many of these functions (collectively referred to as executive functions) have traditionally been considered frontal lobe functions on the basis of well-documented dysfunction in patients with brain damage to the frontal lobes and the premise that the frontal cortex serves as a superstructure over other parts of the cortex.1 The frontal lobes have a central role in human cognition, emotion, and action related to their anatomical connectivity and late evolutionary development.3,5–7 This portion of the cortex is recognized as synthesizing information from other brain regions, so damage in a variety of brain areas may produce these frontal deficits. The use of the term dysexecutive syndrome has clinical utility given the broad range of cognitive and behavioral deficits that fall within the executive domain, and the fact that these neurologic deficits are rarely confined to the frontal lobes.
This review attempts to provide an overview of how executive functioning has been traditionally defined and measured and the neurologic conditions that result in executive impairment. First, there is a discussion of hypothetically dissociable executive functions based on empirical studies of basic operations. This provides an overview of the executive functions and putative anatomical substrates, but does not provide a review of basic attentional and memory systems, which are covered separately in this issue. This is followed by a review of various dysexecutive syndromes in aging and neurologic disease to demonstrate the prevalence of the dysexecutive syndrome given the diffuse nature of neurologic disorders. Finally, a discussion of the relevance of executive deficits identified by formal neuropsychological measures to everyday functioning will be provided. Although it is clear that intact executive functioning is vital to human autonomy and a major determinant of behavior and disability in neurologic disease, it is unclear whether neuropsychological tests are ecologically valid. The concept of developing ecologically valid tests is a rapidly evolving one, in particular related to the dysexecutive syndrome, which may only become apparent under specific environmental circumstances.
COMPONENTS OF EXECUTIVE FUNCTION
Executive functions can be broken down into a number of aspects of intentional activity that require initiation and organizational structure.4 There have been many conceptualizations of the constructs, operations, or functions that may contribute to various stages of an executive process, with the assumption that systematic evaluation of each of these stages provides insight into the overall executive process. Despite the fact that executive functions may take place in any given modality, many conceptualizations describe the stages related to an action.8 Lezak4 highlights the significance of identifying whether an action is intentional and emphasizes the role of executive functions in the capacity to formulate a goal or form an intention. Having the motivation to initiate the behavior is a necessary condition and when absent, can present as apathy or abulia.9 A failure to respond to a stimulus or initiate an action may fall into one of several intentional disorders (for discussion, see Heilman10). Finally, some conceptualize the abulic-hypokinetic disorder, which affects both behavior and cognitive processes as being a central executive deficit. Conversely, behavioral alterations can take the form of behavioral disinihibition, inappropriateness, increased talkativeness, lack of tact, and tendency to joke (Witzelsucht).11
In order to demonstrate mastery over one's environment, one is required to establish and maintain goals over time. This may also require generating alternative plans to maximize the likelihood of meeting a goal, monitoring of internal and external information, and maintenance of information online. Finally, one must simultaneously suppress inappropriate behaviors and avoid derailment by irrelevant stimuli while initiating appropriate responses to changing environmental stimuli. Therefore, adaptation to a complex and changing environment requires a diverse range of functions including problem solving, set-shifting, self-monitoring, initiation, inhibition, planning, and sequencing. In patients with neurologic disease, deficits may be present in any or all of these executive functions, making assessment particularly challenging.
Planning requires the ability to identify and organize the necessary steps required to achieve a goal. These steps can include the ability to conceptualize (look ahead), view one-self and the environment in an objective fashion, generate alternatives, make decisions, and consider sequential and hierarchical ideas.4 Failure can take place in any one of these steps to impair goal achievement, and therefore measuring planning becomes quite complex. Consequently, there are few tests that directly measure planning, although many standard neuropsychological tests (Rey Osterrieth Complex Figure, Block Design and Picture Arrangement subtest of the Wechsler [WAIS-III]) may yield insight into the process of how a subject approaches a task in terms of organization and planning, although the task may be designed to measure some other function. Many paradigms designed to measure planning have used serial order or sequencing tasks, although these executive functions appear to be dissociable. For example, the Picture Arrangement subtest of the WAIS-III requires sequential ordering of a pictorial scene.
Damage to the dorsolateral prefrontal cortex (DLPFC) has been associated with impairments in planning and hypothesis generation.12 The anterior DLPFC has been implicated in maintaining goals in working memory, which allows for the manipulation and control of information held online.13 However, most of the support of prefrontal involvement in planning is related to studies using the Tower of Hanoi or Tower of London.2 These tasks require subjects to plan a series of steps that will allow movement of a set of disks to a goal position. The Tower of Hanoi has an added critical step that requires the cognitive demand of being able to resolve a goal-subgoal conflict, which might require a backward move to eventually meet the goal.2 Although many studies including neuroimaging investigations have supported an association between DLPFC in mediating planning, others have suggested that orbital prefrontal dysfunction is a better predictor of real-world planning.14 Some investigators distinguish between a planning deficit measured by a standard test from planning required to successfully complete a task in everyday activities. Participation in an everyday activity requires coordination of multiple cognitive and behavioral regulatory systems in addition to the contribution of the executive system.15
Cognitive Flexibility and Set-Shifting
A hallmark feature of frontal lobe damage is the failure to adjust behavior appropriately in response to contingencies in the environment.16 This can be related to faulty decision making and dysfunction in how consequences of past actions affect online guidance of behavior.2,17 The orbitofrontal cortex (OFC) has been implicated in the decision-making process, and damage to the OFC may impair the ability to assess the strength of the reward associated with an outcome.18 Deficits to this region can have devastating impact on everyday outcomes related to a faulty decision-making process, although deficits in cognition (including those designed to detect frontal lobe dysfunction) may not be evident on standardized neuropsychological tests.
The OFC is a part of the ventromedial prefrontal cortex (VMF) and has extensive connections with the limbic system (including amygdala), cingulate gyrus, and hippocampus.19 Classic studies in nonhuman primates demonstrated that OFC lesions in monkeys impaired their ability to reverse previously learned contingencies.20 Human studies have also focused on the role of the VMF in influencing emotionally driven decision making, such as gambling.21–23 However, comparison of patients with amygdala and VMF lesions suggests that the amygdala has primary role in decision making and that the roles of the VMF and amygdala may be different.17 In this investigation, the gambling task paradigm was used in an attempt to simulate real-life decisions in terms of uncertainty, reward, and punishment. The patients with amygdala damage, but not prefrontal damage, failed to attach affective attributes to stimuli, although both patient groups performed abnormally on the gambling task.17 Nonetheless, the damage to the VMF has been associated with significant emotional dysfunction and real-world behavioral incompentencies.24
Classic neuropsychological measures of executive function have concentrated on attempting to measure how behavior is modified in response to changing stimuli. The two most common tasks used are the go-nogo task and the Wisconsin Card Sorting Task (WCST). The go-nogo paradigm is discussed in the response inhibition section, although it is understood that cognitive flexibility is a necessary prerequisite in order to perform this task accurately. The WCST test has been studied extensively with neuropsychological and neuroimaging investigations following the original development of this task by Grant and Berg.25,26 The task has been designed to measure abstraction of categories and changing cognitive set under shifting task demands that are not identified to the subject. That is, the subject must infer the appropriate stimulus dimensions for sorting the cards on the basis of limited information provided by the examiner.4 Specifically, the test requires subjects to use feedback regarding their performance to match cards on the basis of either shape, form, or number (for a full description of the task, please refer to Lezak4). There is significant support that patients with frontal lobe lesions (in particular those with prefrontal lesions) perform poorly on the WCST.27 However, damage to other brain regions can also alter performance, suggesting that this is truly an executive task that relies on integration across neural systems.28 Subsequent investigations have demonstrated that although patients with frontal-lobe disease may be more severely impaired on this task in terms of perseveration or inability to shift response sets evident in their tendency to adhere to the same criterion and ignore the examiner's feedback, there is considerable variability between frontal lobe patients.29 Additionally, other studies have demonstrated that patients with nonfrontal lesions (ie, more posterior lesions) may be equally impaired on this task and that within the frontal lesion group, impairment does not appear to be predicted by the part of the frontal lobe that is damaged (for review, see Damasio2). WCST measures multiple dimensions of executive control,12 and performance does not appear to be specific to frontal lobe damage unless deficits in comprehension or visual search are controlled.12,30 Although the WCST is considered the best characterized and well-validated measure of executive control, neither neuroimaging nor factor analyses have localized specific and robust WCST related factors to the frontal lobes. This is most likely because the WCST measures multiple executive functions that result in involvement of widespread frontal regions.
Initiation and Self-Generation
Reduced initiation or latency in responding can alter the productivity of an individual in a variety of capacities. Slowed responding or response failures can occur across a number of cognitive and behavioral domains and may be apparent from family reports of a patient's failure to initiate premorbid activities. It is important that ignition failures related to cognitive deficits not be attributed to the decreased activity and lack of engagement, which can be present in clinical depression. Tests that require either verbal (letter fluency) or nonverbal (design fluency) generation of items (words or novel designs) in a timed condition with specific task constraints have been used to estimate the generational capacity of an individual.4,16,31,32 However, a subject can fail on these tasks related to primary language dysfunction common in left hemisphere lesions or visuospatial or perceptual deficits following right hemisphere damage, making it difficult to discern why the subject failed to generate a number of appropriate responses. Some may argue, however, that speech and language functions involve movement selection and that words are responses generated in the context of both internal and external stimuli.33 The frontal lobes, in particular in the left hemisphere, contain several speech zones that are involved in speech generation. Similarly, the frontal lobe may play a role in providing internal representations of spatial information.16
Investigations of patients with discrete frontal lesions have implicated bilateral superior medial frontal regions as critical for initiating and sustaining responses.31,34 These deficits are in the absence of external triggers or motivational conditions that might elicit responding and therefore refer to responses that are self-generated. This also refers to the ability to sustain a response over a period of time in order to accomplish a goal. Damage to the same regions of the frontal lobe resulted in significantly reduced reaction times on tests of sustained attention and involved supplementary motor area (SMA) and the pre-SMA region.34
Another well-recognized deficit of persons with frontal lobe lesions is failure to inhibit behavioral responses that are inappropriate to the environmental contingencies or fail to lead to successful goal attainment. It is conceivable that failures to inhibit ineffective behavioral responses may be related to inability to learn with repeated trials.35 Problems with response inhibition can be evident in a patient's failure to inhibit inappropriate verbal or behavioral responses and may be best assessed through behavioral observation during a clinical examination and family reports.4,9 This often presents as behavioral impulsivity, which can affect a wide range of everyday behaviors with significant consequences on effective functioning in the real world.12,15
The Stroop test36 is a classic paradigm measuring response inhibition (see Lezak4). The Stroop requires subjects to read color words (ie, blue, green, red) each printed in conflicting colored ink. The task requires the subject to suppress the name of the word and to provide the ink color of the word (eg, the word red printed in blue ink). There is some indication that patients with left frontal lesions are particularly impaired on the Stroop related to their inability to inhibit the habitual response of word reading.37 Conversely, a more recent study identified bilateral frontal as well as right frontal superior posteromedial lesions as associated with increased errors and slowness in response time for the incongruent condition of the Stroop.38 However, this investigation primarily emphasized the maintenance of the activated intention as opposed to inhibition. There is additional evidence from functional magnetic resonance imaging (fMRI) that the Stroop activates the anterior cingulate and its mesiofrontal extensions in a distributed fashion.39 This, in part, is related to the fact that the Stroop measures multiple dimensions of executive control simultaneously.11,39 Other tests, such as Trails B and Digit Span Backwards (see Lezak4 for review and description) have loaded with the Stroop on a single factor of response inhibition, although other investigators have emphasized the mental control aspect as opposed to the inhibitory aspects of these tasks (for review, see Royall and Lauterbach12).
The alternating programs and go-nogo paradigms also measure response inhibition and can be administered at the bedside. These tests often use the regulation of motor responses to determine the ability to maintain a correct response set without perseverations (repetition of a previous response) or failure to inhibit.4 The prefrontal cortex controls our actions in terms of deciding when to initiate and when to withhold a response. For example, if the examiner taps once, the patient must tap twice, but if the examiner taps twice, the patient should tap once.40 Patients with frontal-lobe lesions may duplicate the examiner's response pattern because of failure to inhibit the competing response. Alternatively, if extended to the go-nogo paradigm, they may be asked to withhold any response when the examiner taps twice. Demonstrated failures to withhold a response in frontal lesion patients have been interpreted as impaired response inhibition.4 Impairment on the go-nogo task has been associated with prefrontal lesions in both animals and humans11,41 and recently more specifically with lesions to the superior medial frontal region (including the SMA).42
Based on clinical observations, lesions in the orbitofrontal and medial frontal areas (ie, parts of frontal lobe containing paralimbic cortex) are associated with behavioral disinhibition and poor emotional regulation. The OFC and cingulate gyrus have reciprocal connections with the limbic system and work together to regulate emotional responses and experiences (for review, see references 2,9,43). Both deficient emotional systems and lack of online behavior monitoring have been proposed to account for the inappropriately familiar interactions orbitofrontal patients have with strangers.44 One approach to assessment has been to identify behavioral sequelae of executive dyscontrol using behavioral rating scales such as the Neuropsychiatric Inventory45 and the Behavioral Assessment of the Dysexecutive Syndrome (BADS).46 The Frontal Lobe Personality Scale,47 which is now referred to as the Frontal Systems Behavior Scale, has established validity and reliability for assessing behaviors associated with frontal lobe damage including apathy and disinhibition. Apathy has been associated with difficulty in basic activities of daily living, suggesting that behavioral scales of frontal behavioral disorders may provide predictive information determining daily functioning, over and above that available from cognitive tests.18,49
Serial Ordering and Sequencing
The relationship between motor regulation and sequences has long been considered a frontal lobe function. Alexander Luria40 was the first to incorporate motor sequencing tasks into neuropsychological assessments as a means of measuring the integrity of the frontal lobes. The classic tasks have been rapid finger sequencing and hand sequencing (fist-edge-palm) and have been demonstrated as very sensitive to the presence of frontal lobe damage.4 There has been some suggestion that left frontal lesions may present with greater deficits in sequencing errors and perseverations.50 However, sequencing or serial order deficits may be evident in other domains such as visuospatial (ie, Picture Arrangement), although this is typically assessed using tests of motor regulation. Sequencing failures in everyday activities such as making a sandwich can significantly affect the level of independent functioning. The neural mechanisms of sequencing and serial ordering and whether these differ for motor and nonmotor systems are unclear despite a strong suggestion of frontal mediation.
According to Passingham,33 the premotor region selects behavioral responses relative to external cues, while the SMA selects responses that rely on internal cues. Generation of movements involving complex sequencing, in particular, have been demonstrated to be mediated by the SMA.51 Others have suggested that it is the internally driven nature of self-paced movements and not sequencing that the SMA primarily mediates.52 Deiber et al52 demonstrated that the premotor cortex plays a role in movement sequences only when triggered by an external cue. Finally, Jenkins53 compared performance of prelearned movement sequences to the learning of a sequence and demonstrated that the SMA had greater activation during the prelearned sequence, while the lateral premotor region was more activated during the acquisition of a sequence. It is conceivable that generation of prelearned sequences relies more heavily on internal cues, while learning of sequences relies on external cues.
PROFILES IN AGING AND NEUROLOGIC DISEASE
Profiles of frontal-executive dysfunction have largely been obtained from investigations of patients with frontal lesions from either vascular disease or other pathologies such as tumors. The demonstrated deficits of patients with frontal lesions were related to the anatomical areas damaged and have provided the neuroanatomical basis for frontal-executive deficits reviewed in this paper (for review, see Damasio and Anderson2). However, white matter lesions related to small vessel ischemic disease impair executive functions regardless of their location.54 Different neuropathologic conditions have a predilection for specific brain regions or circuits and therefore may present with distinct cognitive profiles with respect to the executive system. The following is a review of executive deficits in aging, traumatic brain injury (TBI), frontotemporal dementia (FTD), and Parkinson's disease (PD), some of the common neurologic conditions that present with frontal-executive dysfunction.
Although memory decline is the most prominent cognitive feature of aging, there is behavioral and neurobiological evidence that multiple distinct factors contribute to memory decline.55 In addition to memory difficulties, deficits on tasks of attention and executive abilities have been demonstrated in studies of healthy aging.55–59 One conceptualization of age-related memory decline makes a distinction between memory decline related to executive dysfunction and frontal atrophy and decline in long-term declarative memory reflective of medial temporal atrophy.55,56 There is well-documented cognitive decline in areas of speed of information processing, cognitive flexibility, and executive functions in healthy nondemented adults.55–58
Studies of healthy aging have identified age-associated decreases in brain volume, in particular in the frontal gray matter and the subcortical regions. Furthermore, frontal gray matter volumes in lateral frontal regions have been associated with the ability to plan, organize, and execute strategies and have been demonstrated to vary across the life span.60 Some investigators emphasize changes in frontal-striatal circuits as contributing more significantly to age-associated executive decline, related to the presumed vulnerability of white matter in aging.55 Neuroimaging investigations using structural MRI have correlated extent of white matter lesions with severity of executive deficits (for review, see references 61,62). A recent investigation comparing gray matter volumes in frontal and subcortical regions demonstrated that the anterior cortical brain regions had the most prominent volume reduction, although other age-associated volume reductions were evident in subcortical regions including the striatum.60 However, the frontal aging hypothesis is certainly not without controversy.63,64 In particular, the controversy is regarding whether age-related cognitive changes are selective (ie, executive deficits) and whether the frontal cortex (in particular the prefrontal cortex) is more vulnerable. Proponents of the frontal aging hypothesis argue that support lies in demonstrated early decline in prefrontal functions compared to nonfrontal regions, in particular on tasks such as the Stroop, which has demonstrated greater interference for older adults.63
Traumatic Brain Injury
The frontal systems are vulnerable to damage following TBI related to both diffuse axonal injury and cortical frontal contusions.65,66 The frontal lobes are susceptible to injury following TBI related to both direct blows to the skull (motor vehicle accidents are more likely to affect the frontal region) or acceleration/deceleration forces.67 These forces can cause the brain to be damaged related to ridges and bony confines of the skull that are protruding. These contusions may affect the basofrontal and anterobasal temporal regions and less commonly the dorsolateral prefrontal cortex.15 Diffuse axonal injury is diffuse microscopic shearing of axons and blood vessels that primarily affects white matter,65 but it may also involve subcortical structures with frontal projections.68 Because of the interconnections between the lateral frontal and posterior regions, diffuse pathology such as axonal injury can cause executive dysfunction.15 Neuroimaging studies (MRI and diffusion tensor) have documented the association between the presence of diffuse axonal injury and persistent cognitive impairment, primarily in the executive domain.65
In TBI, disturbances of executive function can be accompanied by changes in personality or problems with self-awareness and behavioral self-regulatory functions, which have been associated with damage to the inferior medial frontal cortex and frontal polar regions, respectively.15 Self-regulatory dysfunction can take the form of difficulty in comprehending the emotional consequences of behavior, behavioral disinhibition, or self-awareness involving the inability to be aware of one's own mental state. This can also be evident in appreciation of humor, the ability to take another individual's perspective, and use appropriate judgment in social behavior. Some investigations have suggested that the personality and behavioral changes following TBI are greater barriers to successful reintegration than cognitive sequeale.15
Dementia syndromes can be caused by a number of different etiologies, although this section focuses on the most common neurodegenerative processes associated with executive dysfunction and behavioral compromise, FTD. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), a dementia is defined as multiple cognitive deficits that typically include memory impairment and at least one other cognitive impairment that have a direct impact on independence in daily functioning.69 Disturbances of executive dysfunction are common disturbances in dementia syndromes including Alzheimer's disease. However, unlike prominent memory deficits in Alzheimer's disease, FTD can present with executive dysfunction or personality alterations related to the affected anatomy in the disease process.70,71 The onset is also about a decade earlier than that of Alzheimer's disease.72
FTD is a progressive neurodegenerative syndrome that was originally described as atrophy in the frontal and temporal regions.73 It has diverse clinical presentations as well as varied underlying histopathology, which is beyond the scope of this paper and requires further validation (for review, see Grossman74). Given the variable clinical presentations, there have been some attempts to devise subtypes of disorders based on common presentations of neurobehavioral disorder or progressive aphasia.75 One subtype that has received partial validation includes a dysexecutive syndrome and behavioral and personality deficits evident in social conduct, insight, impulsivity, disinhibition, mental flexibility, distractibility, and perseveration. This can also present as emotional unconcern, apathy, and failure to initiate tasks.74 Other features can include hyperorality, hypersexuality, and unprovoked rage behavior.76 The presenting features of rigidity, inflexibility, disinhibition and impulsivity, distractibility, and perseverative behavior may also affect their executive functioning.74 They can become echopraxic and echolalic and present with utilization behavior (ie, the tendency to pick up and use irrelevant objects) and be stimulus bound.9,77 Neuroimaging studies have identified a number of brain regions that may be affected in FTD including orbitofrontal, dorsolateral frontal, and anterior temporal areas.78 One single-photon emission computed tomography investigation identified that perfusion was particularly reduced in orbitofrontal and anterior temporal regions in patients with FTD compared to Alzheimer's disease.79
PD is a neurodegenerative disorder believed to be caused by dopaminergic depletion in the nigrostriatal system. The hallmark features of the disease are motor deficits of bradykinesia, rigidity, and tremor, although cognitive and behavioral features are well documented.80–82 The cognitive and behavioral impairments in PD are similar to those in patients with frontal and basal ganglia lesions, suggesting that frontostriatal circuit dysfunction is responsible.83,84 A number of deficits in executive functions have been identified in PD including behaviors required for planning and problem solving, such as goal-directed behavior, the ability to generate multiple response alternatives, maintenance of response set, and the ability to evaluate and modify behavior.83,85 Executive dysfunction has been demonstrated in early PD, in nondemented patients, and includes deficits in executive motor planning, slowness in problem solving, and set-shifting.83,85
The cognitive deficits evident in PD are thought to be related to disruption of several anatomically and functionally distinct circuits that link the frontal cortex with subcortical structures.84,86,87 Several parallel circuits have been proposed, including those involved in the regulation of movement and those involved in cognitive processes such as executive function, which is regarded as the primary cognitive sequelae in this disease.84,86,87 Three complex circuits have been proposed as relevant to the nonmotor symptoms identified in PD. The following three circuits are related to three frontal cortical regions and associated cognitive and behavioral functions: (1) anterior cingulate cortex regulates response initiation, intention, inhibition, and conflict monitoring; (2) the DLPFC mediates set-shifting, complex problem solving, organizational strategies, and working memory; (3) the OFC has been associated with behavioral monitoring including disinhibition, making decisions based on reinforcement/reward schedule to maintain a behavioral set, impulse control, and mood and personality changes.86–88
Despite these well-delineated circuits hypothetically underlying cognitive symptoms of PD, the neurochemical and neuroanatomical basis of cognitive symptoms in PD are poorly understood. This in part is related to the variability in cognitive deficits and the lack of full correlation with motor symptoms and disease severity. Additionally, a subset of PD patients may present with additional Alzheimer's pathology, while some patients with parkinsonian features may be misclassified as having idiopathic PD when they have an atypical neurodegenerative disorder. Therefore, difficulties with clinical diagnostic categories involving disorders with extrapyramidal features may obscure clear understanding of the cognitive manifestations of idiopathic PD.
The Impact of Executive Deficits on Everyday Functioning
Everyday functioning places tremendous demands on the executive system in order for an individual to conduct him- or herself in an efficient and appropriate fashion.89,90 However, the nature of standard tests is very different from the requirements in daily activities.46 Real-life complex situations (eg, shopping, preparing a meal) require organization and structuring of goal-related behavior and therefore require a number of different cognitive resources.91 Consequently, some patients may perform flawlessly on standardized tests of executive function, but have impairment in everyday functioning.92 This suggests that there may be a set of critical processes required for competency in multitasking in everyday life that is not measured by standardized tests.91 Conversely, some patients may demonstrate cognitive impairment on standardized tests, but compensate for their difficulties in such a way that everyday functioning is relatively preserved.93 The ability to compensate may be largely related to the external demands placed on the individual as well as the cerebral reserve that is available (ie, the intelligence of the individual).
The term ecological validity has been used to refer to the representativeness of a task or how a clinical task relates to a situation encountered outside the laboratory.46,94 Ecological validity has become an increasingly important focus for the executive functions that coordinate cognitive and behavioral capacities with real-world demand situations.95 Traditional tests of executive function have been developed based on experimental investigations and have provided limited clinical applications and poor generalizability to everyday functions.96 Most experimental and neuropsychological measures focus on measuring constructs by identifying the underlying neural operation, with little consideration of how this affects real life. Furthermore, it is conceivable that impaired emotional regulation that often accompanies frontal lobe syndromes can influence real-life function even in the absence of cognitive failures.97 Therefore, in clinical practice, interviews with family and caregivers may provide insights into behavioral appropriateness and daily functioning, similar to assessments of activities of daily living that typically rely on ratings by caregivers.
Patients with frontal executive deficits encounter real-life problems in social situations and may be incapable of generating appropriate responses. Another hypothesis regarding why patients with frontal lesions encounter real-life problems is that these patients fail to select the most advantageous choice in a range of response options.2 There have been some previous attempts to assess patients in terms of their everyday planning skills such as devising situations where a subject must negotiate an awkward situation.98 Patients with more anterior lesions (relative to posterior lesions) demonstrated inability to generate a range of plausible solutions. Also, patients with prefrontal lesions took much longer than normal subjects to make financial decisions.99 They demonstrated inability to identify information that was missing from the problem scenario and poor judgment regarding the adequacy of their plans. There is some evidence that the inability to develop logical strategies and to execute complex plans may be correlated with behavioral problems (in particular motivational changes).94,100 This implies that a complete assessment poised to identify daily failures should include a behavioral assessment. One example of such a scale is the Behavior Rating Inventory of Executive Function (BRIEF), which was developed to capture the real-world behavioral manifestations of the dysexecutive syndrome.95
In a recent paper, Burgess et al96 discuss the recommendation that “function-led” executive tests should be developed for the specific intention of clinical application. This would be in direct contrast to the general practice of adapting procedures from experimental investigations. The traditional tests of frontal lobe dysfunction have been criticized for failing to provide direct evidence of the existence of basic operations of frontal systems and the fact that they are remote from and not informative about clinical functional failure.94,96 Burgess et al94 define functions as directly observable behavior that is the product of a series of operations (many experimental observations are operations) and that allows clear identification of success or failure based on whether a goal has been met. Ecological assessment of executive functions in neurologic disease may have important applications for prediction of treatment outcomes and everyday functioning and rehabilitation.91 Some investigators argue that these measures may be more discriminative than traditional tests of executive function.92
There have been several recent attempts to develop executive tests with greater ecological validity.46,93,100 The BADS has demonstrated greater discriminative power for predicting occupational status than a traditional executive test.46 This test was designed to overcome deficiencies in standard executive tests by including items sensitive to skills in problem solving, planning, and organizing behavior over an extended period of time and thus taps capacities that are used in everyday living. This battery of tests is composed of several subtests designed to assess six problem errors common to the dysexecutive syndrome (temporal judgment, set-shifting, problem solving, strategy formation, planning, and monitoring).46 Many of the more recent attempts to evaluate executive deficits in everyday life have capitalized on the conceptualization of the BADS and/or adapted one or more of the subtests to a specific neurologic population.93,100
Alderman et al93 also devised a multiple errands shopping test that evaluated multitasking in a general neurologic population. They identified two clear patterns of failure characterized by rule breaking or failure to achieve tasks. They interpreted these findings as supportive of two independent sources of failure: memory failures and problems with initiation.93 Another approach to investigating executive dysfunction has been the analysis of naturalistic actions in everyday tasks such as cooking, which require correct sequential ordering to achieve a goal.7,101–103 These investigations have attempted to resolve questions about the organization of complex, routine action, and the nature of executive dysfunction in predicting which patients make substantial errors in everyday tasks.
Although the relationship between neuropsychological executive tests and naturalistic action has been poorly understood, naturalistic action impairment appears to be associated with increased caregiver burden and decreased functional independence.104 However, the operations identified by ecological means will eventually have to be resolved with the basic operations of frontal systems from experimental procedures. There is a need for research investigations that attempt to investigate frontal executive systems using both tests of basic operations based on previous experimental investigations and novel ecological approaches. This will help identify the critical brain regions and aspects of complex everyday behaviors that lead to failure to meet a goal.
SUMMARY AND CONCLUSIONS
The frontal lobes have proven to be a complex region to investigate. Despite advances in neuroimaging research, there are still several competing theories about executive functions and the role of the frontal lobes. Since there is no specific neurologic disorder with a predilection to damage isolated to the frontal lobes, investigations have relied on pathology that involves damage to several regions in addition to the frontal lobes. This neurologic reality has helped sustain the controversy surrounding the dysexecutive syndrome and different theoretical positions regarding whether there is indeed a unified dysexecutive syndrome or separate frontal processes that are capable of being fractionated. Furthermore, traditional measures of frontal executive deficits have failed to balance cognitive deficits with behavioral alterations and have been criticized for their lack of ecological validity. For the reasons outlined above, there is tremendous need for ongoing experimental investigations of executive processes.
There is a need for research investigations that attempt to investigate frontal executive systems using both tests of basic operations based on traditional experimental investigations and novel ecological approaches. Further research on the neural underpinnings of basic operations will yield insights into the basic executive operations subserved by distinct brain regions and provide a better understanding of expectations of daily functioning given a specific neurologic condition. Since the process of accomplishing a real-life goal is a multicomponent process requiring intact cognitive and behavioral systems, this approach would allow for improved analysis of the critical cognitive and behavioral predictors of routine everyday tasks required for functional independence. Understanding the critical components of success in routine daily operations will provide salient targets for treatment or rehabilitation in neurologic patients presenting with features of the dysexecutive syndrome.
1. Luria A. The Working Brain. New York: Basic Books, 1973.
2. Damasio A, Anderson SW. The frontal lobes. In: Heilman K, Valenstein E, eds. Clinical Neuropsychology. New York: Oxford University Press, 2003:404–446.
3. Kolb B, Whishaw IQ. The frontal lobes. In: Fundamentals of Human Neuropsychology, Fifth Edition. New York: Worth Publishers, 2003:391–425.
4. Lezak M, Howieson DB, Loring DW. Executive functions and motor performance. Neuropsychological Assessment. Oxford: Oxford University Press, 2004:611–646.
5. Fuster JM. Frontal lobe and cognitive development. J Neurocytol. 2002;31:373–385.
6. Fuster JM. Jackson and the frontal executive hierarchy. Int J Psychophysiol. 2007;64:106–107.
7. Luria AR. Higher Cortical Functions in Man. New York: Basic Books, 1966.
8. Koechlin E, Danek A, Burnod Y, et al. Medial prefrontal and subcortical mechanisms underlying the acquisition of motor and cognitive action sequences in humans. Neuron. 2002;35:371–381.
9. Mesulam MM. Behavioral Neuroanatomy: Principles of Behavioral and Cognitive Neurology. New York: Oxford University Press, 2000:41–54.
10. Heilman KM, Watson RT, Valenstein E. Neglect and Related Disorders. In Heilman KM, Valenstein E (eds). Clinical Neuropsychology, Fourth Edition. Oxford: Oxford University Press, Inc; 2003;296–346.
11. Adams R, Victor M, Ropper AH. Neurologic disorders caused by lesions in particular parts of the cerebrum. Principles of Neurology, 6th ed. New York: McGraw-Hill, 1997:442–448.
12. Royall DR, Lauterbach EC, Cummings JL, et al. Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci. 2002;14:377–405.
13. Koechlin E, Basso G, Pietrini P, et al. The role of the anterior prefrontal cortex in human cognition. Nature. 1999;399:148–151.
14. Sarazin M, Pillon B, Giannakopoulos P, et al. Clinicometabolic dissociation of cognitive functions and social behavior in frontal lobe lesions. Neurology. 1998;51:142–148.
15. Cicerone K, Levin H, Malec J, et al. Cognitive rehabilitation interventions for executive function: moving from bench to bedside in patients with traumatic brain injury. J Cogn Neurosci. 2006;18:1212–1222.
16. Kolb B, Whishaw IQ. The frontal lobes. In: Fundamentals of Human Neuropsychology, 5th Edition. New York: Worth Publishers, 2003:391–425.
17. Bechara A, Damasio H, Damasio AR, et al. Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. J Neurosci. 1999;19:5473–5481.
18. Wallis JD. Orbitofrontal cortex and its contribution to decision-making. Annu Rev Neurosci. 2007;30:31–56.
19. Carmichael ST, Price JL. Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. J Comp Neurol. 1995;363:615–641.
20. Mishkin M. Perseveration of central sets after frontal lesions in monkeys. In: Akert JMWK, ed. The Frontal Granular Cortex and Behaviour. New York: McGraw-Hill, 1964:219–241.
21. Bechara A, Damasio H, Tranel D, et al. Deciding advantageously before knowing the advantageous strategy. Science. 199728;275:1293–1295.
22. Bechara A, Tranel D, Damasio H, et al. Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex. Cereb Cortex. 1996;6:215–225.
23. Damasio AR. The somatic marker hypothesis and the possible functions of the prefrontal cortex. Philos Trans R Soc Lond B Biol Sci. 1996;351:1413–1420.
24. Anderson SW, Barrash J, Bechara A, et al. Impairments of emotion and real-world complex behavior following childhood- or adult-onset damage to ventromedial prefrontal cortex. J Int Neuropsychol Soc 2006;12:224–235.
25. Berg E. A simple objective technique for measuring flexibility in thinking. J Genet Psychol. 1948;39:15–22.
26. Grant D, Berg EA. A behavioral analysis of degree of reinforcement and ease of shifting to new responses in a Weigl-type card sorting problem. J Exp Psychol. 1948;38:404–411.
27. Milner B. Effect of different brain lesions on card sorting. Arch Neurol. 1963;9:90–100.
28. Stuss DT. Frontal lobes and attention: processes and networks, fractionation and integration. J Int Neuropsychol Soc. 2006;12:261–271.
29. Wisconsin Card Sorting Test Manual [computer program]. Odessa, FL: Psychological Assessment Resources, Inc., 1981.
30. Stuss DT, Levine B, Alexander MP, et al. Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes. Neuropsychologia. 2000;38:388–402.
31. Stuss DT, Alexander MP. Is there a dysexecutive syndrome? Philos Trans R Soc Lond B Biol Sci. 2007;362:901–915.
32. Stuss DT, Alexander MP, Hamer L, et al. The effects of focal anterior and posterior brain lesions on verbal fluency. J Int Neuropsychol Soc. 1998;4:265–278.
33. Passingham RE. The Frontal Lobes and Voluntary Action. Oxford: Oxford University Press, 1993.
34. Stuss DT, Alexander MP, Shallice T, et al. Multiple frontal systems controlling response speed. Neuropsychologia. 2005;43:396–417.
35. Cicerone K, Lazar RM, Shapiro WR. Effects of frontal lobe lesions on hypothesis sampling during concept formation. Neuropsychologia. 1983;21:513–524.
36. Stroop J. Studies of interference in serial verbal reactions. J Exp Psychol. 1935;18:643–662.
37. Perret E. The left frontal lobe of man and the suppression of habitual responses in verbal categorical behavior. Neuropsychologia. 1974;12:323–330.
38. Stuss DT, Floden D, Alexander MP, et al. Stroop performance in focal lesion patients: dissociation of processes and frontal lobe lesion location. Neuropsychologia. 2001;39:771–786.
39. Peterson BS, Skudlarski P, Gatenby JC, et al. An fMRI study of Stroop word-color interference: evidence for cingulate subregions subserving multiple distributed attentional systems. Biol Psychiatry. 1999;45:1237–1258.
40. Luria A. Higher Cortical Functions in Man. New York: Basic Books, 1966.
41. Drewe EA. Go-no go learning after frontal lobe lesions in humans. Cortex. 1975;11:8–16.
42. Picton TW, Stuss DT, Alexander MP, et al. Effects of focal frontal lesions on response inhibition. Cereb Cortex. 2007;17:826–838.
43. LeDoux J. The holy grail. In: The Emotional Brain: The Mysterious Underpinnings of Emotional Life. New York: Touchstone, 1996:73–103.
44. Beer JS, John OP, Scabini D, et al. Orbitofrontal cortex and social behavior: integrating self-monitoring and emotion-cognition interactions. J Cogn Neurosci. 2006;18:871–879.
45. Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44:2308–2314.
46. Behavioural Assessment of the Dysexecutive Syndrome [computer program]. Bury St. Edmunds: Thames Valley Test Company, 1996.
47. Paulsen JS, Stout JC, De LA, et al. Frontal behavioral syndromes in cortical and subcortical dementia. Assessment. 1996;3:327–337.
48. Norton LE, Malloy PF, Salloway S. The impact of behavioral symptoms on activities of daily living in patients with dementia. Am J Geriatr Psychiatry. 2001;9:41–48.
49. Stout JC, Wyman MF, Johnson SA, et al. Frontal behavioral syndromes and functional status in probable Alzheimer disease. Am J Geriatr Psychiatry. 2003;11:683–686.
50. Harrington DL, Rao SM, Haaland KY, et al. Specialized neural systems underlying representations of sequential movements. J Cogn Neurosci. 2000;12:56–77.
51. Roland PE, Larsen B, Lassen NA, et al. Supplementary motor area and other cortical areas in organization of voluntary movements in man. J Neurophysiol. 1980;43:118–136.
52. Deiber MP, Passingham RE, Colebatch JG, et al. Cortical areas and the selection of movement: a study with positron emission tomography. Exp Brain Res. 1991;84:393–402.
53. Jenkins IH, Brooks DJ, Nixon PD, Frackowiak RS, Passingham RE. Motor sequence learning: a study with positron emission tomography. J Neurosci. 1994;14:3775–3790.
54. Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location. Neurology. 2004;63:246–253.
55. Buckner RL. Memory and executive function in aging and AD: multiple factors that cause decline and reserve factors that compensate. Neuron. 2004;44:195–208.
56. Hedden T, Gabrieli JD. Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci. 2004;5:87–96.
57. West RL. An application of prefrontal cortex function theory to cognitive aging. Psychol Bull. 1996;120:272–292.
58. Huh TJ, Kramer JH, Gazzaley A, et al. Response bias and aging on a recognition memory task. J Int Neuropsychol Soc. 2006;12:1–7.
59. Moscovitch M, Winocur G. Frontal lobes, memory, and aging. Ann N Y Acad Sci. 1995;769:119–150.
60. Zimmerman ME, Brickman AM, Paul RH, et al. The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan. Am J Geriatr Psychiatry. 2006;14:823–833.
61. Gunning-Dixon FM, Raz N. The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology. 2000;14:224–232.
62. DeCarli C, Scheltens P. Structural brain imaging. In: Erkinjuntti T, Gauthier S, eds. Vascular Cognitive Impairment. London: Martin Dunitz, 2002:433–457.
63. West R. In defense of the frontal lobe hypothesis of cognitive aging. J Int Neuropsychol Soc. 2000;6:727–730.
64. Greenwood PM. The frontal aging hypothesis evaluated. J Int Neuropsychol Soc. 2000;6:705–726.
65. Scheid R, Walther K, Guthke T, et al. Cognitive sequelae of diffuse axonal injury. Arch Neurol. 2006;63:418–424.
66. Adams JH, Doyle D, Ford I, et al. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989;15:49–59.
67. Varney NR, Varney RN. Brain injury without head injury. Some physics of automobile collisions with particular reference to brain injuries occurring without physical head trauma. Appl Neuropsychol. 1995;2:47–62.
68. Adair JC, Williamson DJ, Schwartz RL, et al. Ventral tegmental area injury and frontal lobe disorder. Neurology. 1996;46:842–843.
69. American Psychiatric Association. DSM-IV. Delirium, dementia, and amnestic and other cognitive disorders. In: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, DC: American Psychiatric Press, Inc., 1994:123–163.
70. Jagust WJ, Reed BR, Seab JP, et al. Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia. Am J Physiol Imaging. 1989;4:89–96.
71. Pachana NA, Boone KB, Miller BL, et al. Comparison of neuropsychological functioning in Alzheimer's disease and frontotemporal dementia. J Int Neuropsychol Soc. 1996;2:505–510.
72. Haase G. Diseases presenting as dementia. In: Wells C, ed. Dementia, 2nd ed. Philadelphia: FA Davis, 1977:27–67.
73. Alzheimer A. Uber eigenartige Krankheitsfalle der spateren Alters [On certain peculiar diseases of old age]. Gesante Neurologie Psychiatrie. 1911;4:356–385.
74. Grossman M. Frontotemporal dementia: a review. J Int Neuropsychol Soc. 2002;8:566–583.
75. Mesulam MM, Weintraub S. Spectrum of primary progressive aphasia. Baillieres Clin Neurol. 1992;1:583–609.
76. Cummings JL, Duchen LW. Kluver-Bucy syndrome in Pick disease: clinical and pathologic correlations. Neurology. 1981;31:1415–1422.
77. Shallice T, Burgess PW, Schon F, et al. The origins of utilization behaviour. Brain. 1989;112:1587–1598.
78. Starkstein S, Kremer J. The disinhibition syndrome and frontal-subcortical circuits. In: Lichter D, Cummings JL, eds. Frontal-Subcortical Circuits in Psychiatric and Neurological Disorders. New York: Guilford Press, 2001:163–176.
79. Starkstein SE, Vazquez S, Petracca G, et al. A SPECT study of delusions in Alzheimer's disease. Neurology. 1994;44:2055–2059.
80. Carbon M, Marie RM. Functional imaging of cognition in Parkinson's disease. Curr Opin Neurol. 2003;16:475–480.
81. Zgaljardic DJ, Borod JC, Foldi NS, et al. A review of the cognitive and behavioral sequelae of Parkinson's disease: relationship to frontostriatal circuitry. Cogn Behav Neurol. 2003;16:193–210.
82. Brand M, Labudda K, Kalbe E, et al. Decision-making impairments in patients with Parkinson's disease. Behav Neurol. 2004;15:77–85.
83. Salmon D, Heindel WC, Hamilton JM. Cognitive abilities mediated by frontal-subcortical circuits. In: Lichter D, Cummings JL, eds. Frontal-Subcortical Circuits in Psychiatric and Neurological Disorders. New York: Guilford Press, 2001:114–150.
84. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986;9:357–381.
85. Levin B, Tomer R, Rey G. Clinical correlates of cognitive impairments in Parkinson's disease. In: Huber JC, ed. Parkinson's Disease: Behavioral and Neuropsychological Aspects. New York: Oxford University Press, 1992:97–106.
86. Middleton FA, Strick PL. Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn. 2000;42:183–200.
87. Middleton FA, Strick PLA. Revised neuroanatomy of frontal-subcortical circuits. In: Lichter DG, Cummings JL, eds. Frontal-Subcortical Circuits in Psychiatric and Neurological Disorders. New York: Guilford Press, 2001.
88. Lichter DG, Cummings JL. Fronto-Subcortical Circuits in Psychiatric and Neurological Disorders. New York: Guilford Press, 2001.
89. Wen JH, Boone K, Kim K. Ecological validity of neuropsychological assessment and perceived employability. J Clin Exp Neuropsychol. 2006;28:1423–1434.
90. Zalla T, Plassiart C, Pillon B, et al. Action planning in a virtual context after prefrontal cortex damage. Neuropsychologia. 2001;39:759–770.
91. Burgess PW, Veitch E, de Lacy Costello A, et al. The cognitive and neuroanatomical correlates of multitasking. Neuropsychologia. 2000;38:848–863.
92. Verdejo-Garcia A, Perez-Garcia M. Ecological assessment of executive functions in substance dependent individuals. Drug Alcohol Depend. 2007;90:48–55.
93. Alderman N, Burgess PW, Knight C, et al. Ecological validity of a simplified version of the multiple errands shopping test. J Int Neuropsychol Soc. 2003;9:31–44.
94. Burgess PW, Alderman N, Evans J, et al. The ecological validity of tests of executive function. J Int Neuropsychol Soc. 1998;4:547–558.
95. Gioia GA, Isquith PK. Ecological assessment of executive function in traumatic brain injury. Dev Neuropsychol. 2004;25:135–158.
96. Burgess PW, Alderman N, Forbes C, et al. The case for the development and use of “ecologically valid” measures of executive function in experimental and clinical neuropsychology. J Int Neuropsychol Soc. 2006;12:194–209.
97. Alexander M, Stuss DT. Frontal injury: impairments of fundamental processes lead to functional consequences. J Int Neuropsychol Soc. 2006;12:192–193.
98. Channon S, Crawford S. Problem-solving in real-life type situations: the effects of anterior and posterior lesions on performance. Neuropsychologia. 1999;37:757–770.
99. Goel V, Grafman J, Tajik J, et al. A study of the performance of patients with frontal lobe lesions in a financial planning task. Brain. 1997;120:1805–1822.
100. Allain P, Chaudet H, Nicoleau S, et al. [A study of action planning in patients with Alzheimer's disease using the zoo map test]. Rev Neurol (Paris). 2007;163:222–230.
101. Schwartz MF, Buxbaum LJ, Montgomery MW, et al. Naturalistic action production following right hemisphere stroke. Neuropsychologia. 1999;37:51–66.
102. The Naturalistic Action Test [computer program]. Bury ST. Edmunds: Thames Valley Test Company, 2003.
103. Schwartz MF, Montgomery MW, Buxbaum LJ, et al. Naturalistic action impairment in closed head injury. Neuropsychology 1998;12:13–28.
104. Giovannetti T, Libon DJ, Buxbaum LJ, et al. Naturalistic action impairments in dementia. Neuropsychologia. 2002;40:1220–1232.