Focal Frontal Lobe Lesions Research Articles

The self and self-knowledge after frontal lobe neurosurgical lesions

BackgroundEvidence suggests that damage to the frontal lobes can be associated with changes in cognitive and behavioral functioning and reduced awareness that such changes have occurred. In the current study, the Cognitive Awareness Model was used as a theoretical framework to explore knowledge of the self in people with acquired frontal lesions. MethodsFifteen individuals with focal frontal lobe lesions (FFL) and their nominated informants were compared with fifteen healthy matched control-informant dyads on questionnaire measures designed to assess awareness of difficulties. Questionnaires were adapted to ensure all enabled pre- and post-injury perspectives to be gained from both patient and informant, and to allow novel exploration of awareness of deficits from a third person perspective. ResultsIndividuals with frontal lobe lesions showed adequate awareness of their post-surgery changes, which was substantiated by their informant report. Compared to the control group, the patient group was found to acknowledge more difficulties in current functioning. Perspective-taking ability was limited with both patients and controls being comparatively unreliable in assessing how they were perceived by others. ConclusionThese results demonstrate that FLL patients are engaging in more atypical behaviors compared to healthy controls, but suggest that they are aware of and acknowledge these difficulties. The importance of obtaining multiple viewpoints when examining an individual's level of awareness and the clinical implications of this are discussed.

The left frontal lobe is critical for the AH4 fluid intelligence test

The frontal lobes are thought to make a fundamental contribution to fluid intelligence. However, evidence that fluid intelligence is impaired following focal frontal lobe lesions is surprisingly sparse and based on non-verbal tests of fluid intelligence. We investigated performance on Part 1 of the Alice Heim 4 (AH4–1), a verbal test of fluid intelligence, in a sample of 35 patients with focal, unilateral, left or right, frontal brain tumours and 54 healthy controls. We analysed the following variables: overall number of correct AH4–1 answers, overall AH4–1 accuracy and accuracy on four selected categories of AH4–1 questions that assess abilities previously linked to the frontal lobes, namely: synonyms, verbal analogies, numerical series and multistage calculations. We found several significant frontal effects. Thus, in comparison to healthy controls, frontal patients had a significantly lower overall number of AH4–1 answers, had significantly lower overall AH4–1 accuracy and had significantly poorer performance on verbal analogies and multistage calculations. We also found several significant lateralised left frontal effects. Thus, in comparison to healthy controls, left, but not right, frontal patents had significantly lower overall AH4–1 accuracy and poorer performance on synonyms, numerical series and multistage calculation questions. This suggests that the left frontal lobe plays a critical role in AH4–1 performance. Moreover, left frontal patients had significantly lower overall AH4–1 accuracy and poorer performance on multistage calculations than right frontal patients. These results suggest that a left lateralised frontal network is critically involved in some aspects of fluid intelligence and, in particular, multistage calculations.

Lesions to the Fronto-Parietal Network Impact Alpha-Band Phase Synchrony and Cognitive Control.

Long-range phase synchrony in the α-oscillation band (near 10 Hz) has been proposed to facilitate information integration across anatomically segregated regions. Which areas may top-down regulate such cross-regional integration is largely unknown. We previously found that the moment-to-moment strength of high-α band (10-12 Hz) phase synchrony co-varies with activity in a fronto-parietal (FP) network. This network is critical for adaptive cognitive control functions such as cognitive flexibility required during set-shifting. Using electroencephalography (EEG) in 23 patients with focal frontal lobe lesions (resected tumors), we tested the hypothesis that the FP network is necessary for modulation of high-α band phase synchrony. Global phase-synchrony was measured using an adaptation of the phase-locking value (PLV) in a sliding window procedure, which allowed for measurement of changes in EEG-based resting-state functional connectivity across time. As hypothesized, the temporal modulation (range and standard deviation) of high-α phase synchrony was reduced as a function of FP network lesion extent, mostly due to dorsolateral prefrontal cortex (dlPFC) lesions. Furthermore, patients with dlPFC lesions exhibited reduced cognitive flexibility as measured by the Trail-Making Test (set-shifting). Our findings provide evidence that the FP network is necessary for modulatory control of high-α band long-range phase synchrony, and linked to cognitive flexibility.

Using Virtual Reality to investigate multitasking ability in individuals with frontal lobe lesions

ABSTRACTIndividuals with lesions in the prefrontal cortex often show impairments with the organisation of their behaviour in everyday life. These difficulties can be hard to detect using structured formal tests. The objective of this study was to use Virtual Reality (VR) to explore the multitasking performance of individuals with focal frontal lobe lesions, specifically using the Jansari assessment of Executive Functions (JEF©). Nineteen individuals with frontal lobe lesions were compared with 19 matched controls on the test and a group of commonly used clinical measures of neuropsychological functioning, as well as questionnaire measures of everyday activity, anxiety and depression. There was a significant difference between groups on the overall JEF© score and on five of the eight individual constructs, namely the planning, creative thinking, adaptive thinking, event-based Prospective Memory (PM) and time-based PM constructs. There were no differences between groups on the non-VR EF individual measures apart from on one EF control measure, Trail Making A. These results demonstrate the potential clinical utility of the JEF© and highlight the value of ecologically valid VR measures in detecting impairments in EF in individuals with frontal lobe lesions.

THE NEURAL BASIS OF GENERAL INTELLIGENCE

Professor John Duncan Educated at the University of Oxford (1970–1976) and spent two years at the University of Oregon working with Michael Posner before taking up a research position with...

Impairments in proverb interpretation following focal frontal lobe lesions

The proverb interpretation task (PIT) is often used in clinical settings to evaluate frontal “executive” dysfunction. However, only a relatively small number of studies have investigated the relationship between frontal lobe lesions and performance on the PIT. We compared 52 patients with unselected focal frontal lobe lesions with 52 closely matched healthy controls on a proverb interpretation task. Participants also completed a battery of neuropsychological tests, including a fluid intelligence task (Raven’s Advanced Progressive Matrices). Lesions were firstly analysed according to a standard left/right sub-division. Secondly, a finer-grained analysis compared the performance of patients with medial, left lateral and right lateral lesions with healthy controls. Thirdly, a contrast of specific frontal subgroups compared the performance of patients with medial lesions with patients with lateral frontal lesions. The results showed that patients with left frontal lesions were significantly impaired on the PIT, while in patients with right frontal lesions the impairments approached significance. Medial frontal patients were the only frontal subgroup impaired on the PIT, relative to healthy controls and lateral frontal patients. Interestingly, an error analysis indicated that a significantly higher number of concrete responses were found in the left lateral subgroup compared to healthy controls. We found no correlation between scores on the PIT and on the fluid intelligence task. Overall our results suggest that specific regions of the frontal lobes contribute to the performance on the PIT.

Verbal Episodic Memory Impairment in Schizophrenia: A Comparison with Frontal Lobe Lesion Patients

Schizophrenia (SCZ)-related verbal memory impairment is hypothesized to be mediated, in part, by frontal lobe (FTL) dysfunction. However, little research has contrasted the performance of SCZ patients with that of patients exhibiting circumscribed frontal lesions. The current study compared verbal episodic memory in patients with SCZ and focal FTL lesions (left frontal, LF; right frontal, RF; and bi-frontal, BF) on a four-trial list learning task consisting of three lists of varying semantic organizational structure. Each dependent variable was examined at two levels: scores collapsed across all four trials and learning scores (i.e., trial 4–trial 1). Performance deficits were observed in each patient group across most dependent measures at both levels. Regarding patient group differences, SCZ patients outperformed LF/BF patients (i.e., either learning scores or scores collapsed across trial) on free recall, primacy, primary memory, secondary memory, and subjective organization, whereas they only outperformed RF patients on the semantically blocked list on recency and primary memory. Collectively, these results indicate that the pattern of memory performance is largely similar between patients with SCZ and those with RF lesions. These data support tentative arguments that verbal episodic memory deficits in SCZ may be mediated by frontal dysfunction in the right hemisphere.

Impulsivity and risk-taking behavior in focal frontal lobe lesions

Frontal lobe dysfunction may underlie excessively impulsive and risky behavior observed in a range of neurological disorders. We devised a gambling task to examine these behavior tendencies in a sample of patients who had sustained focal damage to the frontal lobes or nonfrontal cortical regions as well as in a matched sample of healthy control subjects. The main objectives of the study were: (1) to behaviorally dissociate impulsivity and risk-taking; (2) to examine potential associations between specific frontal lesion sites and impulsivity or risk-taking; (3) to investigate the influence of reinforcement and trial timing on both behaviors. Our results indicated that patients and controls were equally likely to perform impulsively. Risk-taking performance strategies, however, were related to left ventrolateral and orbital lesion sites. Moreover, risk-taking was also associated with blunted response alteration following a nonrewarded trial. Patients and control subjects showed identical responses to reward-timing manipulations consistent with formal decision-making theory. These findings suggest that ventrolateral and orbital lesions are related to the reward-based aspects of decision-making (risk-taking) rather than to simple response disinhibition (impulsivity). Reduced reaction to the negative consequences of one's actions may underlie this behavior pattern.

Executive Function Following Focal Frontal Lobe Lesions: Impact of Timing of Lesion on Outcome

While it is generally agreed that outcome following cerebral insult during childhood differs from that seen following similar pathology in adulthood, the specific relationship between timing of cerebral lesion and outcome, and the mechanism associated with observed neurobehavioral changes, remains controversial. Data from children with focal lesions suggests a non-linear relationship between age at injury and language function (e.g., Bates et al., 1999). With respect to executive function, animal models also demonstrate a non-linear relationship, and suggest that outcome is tightly linked to underlying neuronal changes (e.g., Kolb et al., 2000). Whether these models easily translate to humans, where brain morphology, cognitive function and environmental influences are more complex, is not clear. To date, focal lesion research in children has been restricted to individual case studies or, to samples of children with lesions to regions subsuming language function, or those who have undergone hemispherectomy for the treatment of intractable epilepsy. This study aimed to build on current knowledge, investigating executive function in 38 children with focal lesions involving prefrontal cortex. Aetiology and timing of lesions was diverse. Results are consistent with animal research suggesting a non-linear relationship between age at injury and outcome, with “critical periods” during development when the frontal lobes are particularly vulnerable to insult, and others when outcome is more optimal. Our findings indicate that children with prenatal lesions are at greatest risk of neurobehavioral deficits. Children with lesions sustained in middle childhood demonstrate least severe impairments across executive domains, possibly due to a period of peak synaptogenesis and dendritic arborization during this developmental stage, in keeping with animal models and research investigating frontal lobe development.

Episodic Memory in Patients with Focal Frontal Lobe Lesions

Episodic memory was evaluated in patients with unilateral, frontal lobe damage and matched controls using a list- method directed forgetting paradigm. Directed forgetting instructions ( forget vs. remember the word), encoding instructions ( learn vs. judge the word) and test format ( recall vs. recognition) were manipulated in order to explore how variations in encoding and retrieval affect verbal memory. Controls demonstrated a normal directed forgetting effect in recall and less directed forgetting in recognition. Patients with left frontal (LF) damage did not show directed forgetting in either recall or recognition and patients with right frontal (RF) damage showed directed forgetting in recall, but not in recognition. Furthermore, the LF group recalled significantly more of the judge than learn words, suggesting that this group's performance improves by providing them with an encoding strategy. Conversely, the RF group's performance did not depend on encoding instructions and their recognition memory was impaired relative to the other two groups when they were instructed to judge the words. Our results suggest that (a) patients with LF damage show deficits in the rehearsal of to-be-remembered information, (b) whereas patients with RF damage show impairments in recognition memory. Furthermore, both patient groups show a lack of directed forgetting when familiarity-based processes guide performance.

Attentional Inhibition in Patients with Focal Frontal Lobe Lesions

Patients with unilateral, frontal lobe damage and matched controls performed an identity negative priming task as a measure of inhibition in selective attention. Control participants demonstrated a normal negative priming effect, as evidenced by slower reaction times when a previously to-be-ignored item became the target on a subsequent trial (distractor suppression). On the other hand, patients with left medial frontal lobe damage showed positive priming in the distractor suppression condition suggesting facilitation of distractor information. Patients with right frontal lobe damage showed an unreliable pattern of negative priming, some demonstrating an absence of negative priming and others demonstrating enhanced negative priming in the distractor suppression condition. Neither patient group nor controls demonstrated slower responses on a target-to-distractor condition included to evaluate a noninhibitory (i.e., episodic retrieval) account of negative priming. Taken together, our results suggest that (a) the negative priming effect represents active inhibition of a distractor representation, rather than a noninhibitory mismatch between retrieval episodes, and (b) that the frontal lobes, especially the left frontal lobes, contribute to this active inhibition. This research was supported by the Epilepsy Foundation through the generous support of the American Epilepsy Society and by an American Psychological Association Dissertation Research Award

Does Damage to the Frontal Lobes Produce Impairment in Memory?

There has long been controversy about the function of the frontal lobes in memory. Historically, in lesion studies, the frontal lobes were discussed as if they represented a single functional unit, and little attention was paid to possible regional differences. In a series of experiments involving patients with focal frontal lobe lesions, we have demonstrated that different frontal regions affect strategic memory processes in unique ways. In addition, some regions of the frontal lobes are involved in nonstrategic memory encoding, likely through actual involvement of the limbic memory regions or through the impact of processing deficits related to the specific mode of the information to be learned (e.g., language). These findings converge with those of functional imaging studies showing the dissociation of memory processes within the frontal lobes, and are indicative of the complex roles subserved by the frontal lobes. Future research will need to explore how the different functions within the frontal lobes influence other dynamic cognitive systems.

A Meta-Analytic Review of Verbal Fluency Deficits in Depression

A prominent view in the neuropsychological literature is that depression is particularly associated with deficits in executive control processes. A meta-analysis of 42 studies with 2206 participants was therefore conducted to investigate the sensitivity of tests of verbal fluency to the presence of this disorder, as there is a great deal of evidence that these measures are valid markers of executive dysfunction. When the methodology adopted by other meta-analytic reviews was employed, semantic fluency deficits were found to be substantially larger than phonemic fluency deficits. However, when a more rigorous method of meta-analysis was adopted, this indicated that the measures are in fact broadly equivalent in their sensitivity to depression, as has been found for patients with focal frontal lobe lesions. However, in contrast to patients with focal frontal lobe injuries, neither deficit qualified as a differential deficit relative to psychomotor speed. Therefore, for patients with depression, deficits on tests of phonemic and semantic fluency may not reflect executive dysfunction, but a more generalized impairment. Evidence is presented that tests of phonemic and semantic fluency may aid in the differential diagnosis of patients with depression and those in the early stages of dementia of the Alzheimer’s type.

Pathological Laughing and Crying Following Traumatic Brain Injury

The authors examined the prevalence and clinical correlates of pathological laughing and crying (PLC) using the Pathological Laughter and Crying Scale (PLAC) in 92 consecutive patients with acute symptoms 3, 6, and 12 months after traumatic brain injury (TBI). The prevalence of PLC during the first year after TBI was 10.9%. Compared to patients without PLC, patients with PLC had significantly more depressive, anxious, and aggressive behaviors and had poorer social functioning. Additionally, PLC was associated with the presence of anxiety disorder, and focal frontal lobe lesions, especially in the lateral aspect of the left frontal lobe. Findings revealed that prefrontal regulation of limbic circuits may be involved in the pathophysiology of this disturbed emotional expression.

Asymmetrical involvement of frontal lobes in social reasoning.

The frontal lobes are widely implicated in logical reasoning. Recent neuroimaging studies suggest that frontal lobe involvement in reasoning is asymmetric (L>R) and increases with the presence of familiar, meaningful content in the reasoning situation. However, neuroimaging data can only provide sufficiency criteria. To determine the necessity of prefrontal involvement in logical reasoning, we tested 19 patients with focal frontal lobe lesions and 19 age- and education-matched normal controls on the Wason Card Selection Task, while manipulating social knowledge. Patients and controls performed equivalently on the arbitrary rule condition. Normal controls showed the expected improvement in the social knowledge conditions, but frontal lobe patients failed to show this facilitation in performance. Furthermore, left hemisphere patients were more affected than right hemisphere patients, suggesting that frontal lobe involvement in reasoning is asymmetric (L>R) and necessary for reasoning about social situations.

Inhibitory attentional control in patients with frontal lobe damage

The performance of a group of frontal lobe lesion and a group of frontal lobe dementia patients was compared with the performance of their respective matched normal control groups on two tests of inhibitory attentional control—the stop-signal reaction time task and a negative priming task. Both patient groups responded significantly slower than their respective normal control groups, but they showed only marginally significant selective impairments on the measures of inhibition. The data suggest that the specific inhibitory processes evaluated by these two tests are, in general, spared in patients with focal frontal lobe lesions or frontal lobe degeneration.

Laboratory investigations and treatment in frontotemporal dementia.

Alzheimer’s disease (AD) patients. 3 The pattern and degree of focal atrophy was investigated in 17 patients with nonfluent PPA, 11 FTD patients, and 24 probable AD patients, using a computer-automated volumetry and compared to cognitive impairment (T. Fukui and A. Kertesz, presentation at conference). Regional total brain volume ratios showed that the right frontal lobe was significantly smaller in patients with FTD ( p 0.001) and that the biparietal ratios tended to be smaller in patients with AD. When the frontotemporo-central regions were combined to represent the anterior brain, the left anterior brain ratio was significantly smaller in patients with PPA ( p 0.01). Generally, verbal functions represented by the Western Aphasia Battery, the Dementia Rating Scale (DRS), or verbal IQ for the Wechsler Adult Intelligence Scale Revised correlated mainly with left frontal, temporal, and central regional volume; the performance IQ was associated with bilateral frontotemporal and right parietal volume. These results support a view that the behavioral presentation of FTD is associated with right frontal atrophy and that left-sided perisylvian atrophy is a feature of PPA. 5 Volumetric measurements were compatible with the actual clinical diagnoses in more than 70% of the patients. Functional Imaging A positron emission tomography study was conducted to address the question of a specific organization for behavioral and affective behaviors in the frontal lobes (M. Sarazin et al, conference paper). A previous study of brain activity at rest had shown a double dissociation between cognitive performance and behavioral scores in patients with frontal lobe lesions. 6 Performance in executive tasks was correlated only with the regional glucose metabolism of the dorsolateral prefrontal cortex, whereas behavioral disturbances scored by a family informant were specifically associated with the orbitofrontal cortex. In this study, a total of 27 patients, or 15 with the behavioral presentation of FTD and 12 with focal frontal lobe lesions (4 right, 5 left, and 3 bilateral), were included. Behavioral disturbances were evaluated by administering the Lhermitte and colleagues’ scale 7 to the patient informants; the scale consists of 80 questions regarding 16 behavioral items. When 18 F-fluorodeoxyglucose high-resolution positron emission tomography was performed at rest, significant negative correlations were found between glucose metabolism in the orbitofrontal cortex and Brodmann’s area 10 bilaterally, and behavioral deficits such as apathy (with a correlation coefficient that reaches 0.93 in right medial area 10), stereotypy, euphoria, disinterestedness, dependence on the social and physical environment, indifference to rules, attention and programming deficits, and loss of intellectual control. Metabolic values in amygdala highly correlated with impulsiveness, personality disturbances, and loss of emotional control. The right frontal lobe was more implicated than the left one in behavioral and emotional control. Social and mental disinhibition, corresponding to stereotypy, indifference to rules, and loss of intellectual control, were strongly associated with hypometabolism in right orbitofrontal cortex. Impaired affective and emotional control, corresponding to impulsivity, personality changes, and loss of emotional control (including irritability, increased anger, and fre

Face memory impairments in patients with frontal lobe damage

To determine whether damage to prefrontal cortex is associated with face memory impairment. Neurophysiologic and functional imaging studies suggest that prefrontal cortex is a key component of a distributed neural network that mediates face recognition memory. However, there have been few attempts to examine the impact of frontal lobe damage on face memory performance. Patients with focal frontal lobe lesions and normal control subjects were administered two-alternative forced-choice and single-probe "yes/no" tests of recognition memory for novel faces. Retrograde memory was assessed by using famous faces as stimuli. Compared with control subjects, patients with frontal lobe lesions showed evidence of marked anterograde and relatively mild retrograde face memory impairment. In addition, patients with right frontal lesions demonstrated increased susceptibility to false recognition, consistent with the breakdown of strategic memory retrieval, monitoring, and decision functions. Prefrontal cortex plays an important role in the executive control of face memory encoding and retrieval. Left and right prefrontal regions seem to make different contributions to recognition memory performance.

Executive functions and the frontal lobes: a conceptual view.

Several problems in understanding executive functions and their relationships to the frontal lobes are discussed. Data are then presented from several of our studies to support the following statements: (1) the examination of patients with focal frontal lobe lesions is a necessary first step in defining the relation of executive functions to the frontal lobes; (2) there is no unitary executive function. Rather, distinct processes related to the frontal lobes can be differentiated which converge on a general concept of control functions; (3) a simple control-automatic distinction is inadequate to explain the complexity of control-automatic processes; (4) the distinction between complex and simple tasks cannot explain the differences in functions between the frontal lobes and other brain regions; and (5) the most important role of the frontal lobes may be for affective responsiveness, social and personality development, and self-awareness and unconsciousness.

Planning impairments in frontal lobe dementia and frontal lobe lesion patients

Patients with frontal lobe brain damage are reportedly impaired on tasks that require plan development and execution. In this study, we examined the performance of 15 patients diagnosed with frontal lobe dementia and 14 patients with focal frontal lobe lesions on the Tower of London planning task. Patients with frontal lobe dementia committed a significantly higher number of rule violations, made more moves, and demonstrated longer solution time latencies compared to their matched controls. Patients with frontal lobe lesions demonstrated significantly delayed solution times and also made more moves compared to their matched controls. Frontal lobe lesion patient performance suggests an impairment in execution-related processes, while frontal lobe dementia patients appear to be impaired in both plan development and execution. Despite these findings, the identification of a specific cognitive impairment that induces these planning problems remains elusive.