Distinct performance profiles on the Brixton test in frontotemporal dementia

The Brixton Spatial Anticipation Test is a well-established test of executive function that evaluates the capacity to abstract, follow, and switch rules. There has been remarkably little systematic analysis of Brixton test performance in the prototypical neurodegenerative disorder of the frontal lobes: behavioural variant frontotemporal dementia (bvFTD) or evaluation of the test’s ability to distinguish frontal from temporal lobe degenerative disease. We carried out a quantitative and qualitative analysis of Brixton performance in 76 patients with bvFTD and 34 with semantic dementia (SD) associated with temporal lobe degeneration. The groups were matched for demographic variables and illness duration. The bvFTD group performed significantly more poorly (U = 348, p < .0001, r = .58), 53% of patients scoring in the poor–impaired range compared with 6% of SD patients. Whereas bvFTD patients showed problems in rule acquisition and switching, SD patients did not, despite their impaired conceptual knowledge. Error analysis revealed more frequent perseverative errors in bvFTD, particularly responses unconnected to the stimulus, as well as random responses. Stimulus-bound errors were rare. Within the bvFTD group, there was variation in performance profile, which could not be explained by demographic, neurological, or genetic factors. The findings demonstrate sensitivity and specificity of the Brixton test in identifying frontal lobe degenerative disease and highlight the clinical value of qualitative analysis of test performance. From a theoretical perspective, the findings provide evidence that semantic knowledge and the capacity to acquire rules are dissociable. Moreover, they exemplify the separable functional contributions to executive performance.     

Executive Control Functions in Degenerative Dementias: A Comparative Review

This paper reviews the literature concerning executive control impairments in degenerative dementias. The construct of executive control functioning is examined, as is the neuroanatomy of frontal–subcortical networks, believed to underlie executive function (EF) impairments. The pattern of EF impairments in Alzheimer's disease (AD) which affects temporal and parietal brain regions most severely is contrasted with observed executive dysfunctions in patients with dementias involving degeneration of primarily frontal and frontal–subcortical brain areas. EF impairments are present in each of these types of dementing illnesses. Although EF impairments are present in AD, they are less prominent than the memory disorder in the neuropsychological profile of the disease and tend to become more pronounced later in the course of the illness. In contrast, patients with frontal or frontal–subcortical dementia may demonstrate executive dysfunction, which occurs earlier in the disease progression and may be initially more severe.     

CT scan and neuropsychological correlates of Alzheimer's disease and Huntington's disease

"Cortical" and "subcortical" dementia syndromes differ in areas of primary neuropathology and clinical characteristics. Conventional CT scan interpretation, visual inspection of pictures, has not been useful in studying dementia. Recent studies of the digitally stored CT attenuation values have found systematic variations with normal aging and aphasia subtypes. In this study of numerical CT scan information in four Alzheimer's Disease and two Huntington's Disease patients, a double dissociation of frontal and temporal lobe density values was found, and a significant correlation was found between left temporal lobe density and verbal ability measures in the Alzheimer's Disease patients.     

Emotional processing following cortical and subcortical brain damage: contribution of the fronto-striatal circuitry

The present study examined the differential contribution of cortical and subcortical brain structures in emotional processing by comparing patients with focal cortical lesions (n = 32) to those with primarily subcortical dysregulation of the basal ganglia (Parkinson's disease n = 14). A standardized measure of emotional perception (Tübingen Affect Battery) was used. Only patients in the more advanced stages of Parkinson's disease and patients with focal damage to the (right) frontal lobe differed significantly from controls in both facial expression and affective prosody recognition. The findings imply involvement of the fronto-striatal circuitry in emotional processing.     

Les capacités d'inhibition : une fonction « frontale » ?

It has been strongly suggested that one important function related to frontal lobes is inhibition. However, a review of the literature on classical tests of inhibition (Stroop test, WCST, and AB-AC learning) suggests that this hypothesis is not well established. We further examined this hypothesis using short-term and long-term directed forgetting tasks (Reed, 1970, Zacks et al., 1996), the Stroop test and the Hayling test (Burgess and Shallice, 1996) in 13 patients with focal frontal lesions. The results revealed short-term and long-term memory deficits and a slowing down, but no inhibition deficit compared with control subjects. These results question the relevance of the hypothesis of the frontal lobe as the unique substrate of inhibitory mechanisms. More generally, they address the issue of executive functions: are these sustained by the frontal cortex or by a cortical and subcortical diffuse neural network?     

Semantic dementia and persisting Wernicke's aphasia: linguistic and anatomical profiles

Few studies have directly compared the clinical and anatomical characteristics of patients with progressive aphasia to those of patients with aphasia caused by stroke. In the current study we examined fluent forms of aphasia in these two groups, specifically semantic dementia (SD) and persisting Wernicke’s aphasia (WA) due to stroke. We compared 10 patients with SD to 10 age- and education-matched patients with WA in three language domains: language comprehension (single words and sentences), spontaneous speech and visual semantics. Neuroanatomical involvement was analyzed using disease-specific image analysis techniques: voxel-based morphometry (VBM) for patients with SD and overlays of lesion digitized lesion reconstructions in patients with WA. Patients with SD and WA were both impaired on tasks that involved visual semantics, but patients with SD were less impaired in spontaneous speech and sentence comprehension. The anatomical findings showed that different regions were most affected in the two disorders: the left anterior temporal lobe in SD and the left posterior middle temporal gyrus in chronic WA. This study highlights that the two syndromes classically associated with language comprehension deficits in aphasia due to stroke and neurodegenerative disease are clinically distinct, most likely due to distinct distributions of damage in the temporal lobe.     

One size does not fit all: face emotion processing impairments in semantic dementia, behavioural-variant frontotemporal dementia and Alzheimer's disease are mediated by distinct cognitive deficits

Patients with frontotemporal dementia (both behavioural variant [bvFTD] and semantic dementia [SD]) as well as those with Alzheimer's disease (AD) show deficits on tests of face emotion processing, yet the mechanisms underlying these deficits have rarely been explored. We compared groups of patients with bvFTD (n = 17), SD (n = 12) or AD (n = 20) to an age- and education-matched group of healthy control subjects (n = 36) on three face emotion processing tasks (Ekman 60, Emotion Matching and Emotion Selection) and found that all three patient groups were similarly impaired. Analyses of covariance employed to partial out the influences of language and perceptual impairments, which frequently co-occur in these patients, provided evidence of different underlying cognitive mechanisms. These analyses revealed that language impairments explained the original poor scores obtained by the SD patients on the Ekman 60 and Emotion Selection tasks, which involve verbal labels. Perceptual deficits contributed to Emotion Matching performance in the bvFTD and AD patients. Importantly, all groups remained impaired on one task or more following these analyses, denoting a primary emotion processing disturbance in these dementia syndromes. These findings highlight the multifactorial nature of emotion processing deficits in patients with dementia.     

Differential Diagnosis of the Major Progressive Dementias and Depression in Middle and Late Adulthood: A Summary of the Literature of the Early 1990s

There is a preponderance of research on the neuropsychology of the various dementias. There are also direct comparisons between two or more dementias available in the literature. This paper sought to summarize the most recent literature, primarily from 1990 through mid-1996, including recent reviews of the literature from previous decades. The purpose was to provide, in one location, a summary of neuropsychological (i.e., cognitive, motor, and psychiatric) characteristics of major noninfectious, progressive dementias and depression of middle and late adulthood. It is hoped that this review, particularly a summary table provided, will serve as a guide in the differential diagnosis of the dementias by clinicians. In addition to Alzheimer's disease, vascular dementias, Parkinson's disease, Lewy body dementia, Huntington's disease, and frontal lobe dementia, the impact of depression on cognitive functioning is covered given the frequency with which neuropsychologists are asked to differentiate depression from primary dementia.     

Pattern of intrusions in verbal recall: comparison of Alzheimer's disease, Parkinson's disease, and frontal lobe dementia

Although some researchers have suggested that intrusions in word list learning are more frequent in Alzheimer's disease, recent studies have shown that this might not be true. In fact, intrusions are common in many neurological degenerative diseases. The goal of the present study was to examine the types of intrusions made by three groups of patients, namely patients with Parkinson's disease (PD), Alzheimer's disease (AD), and dementia with prominent frontal lobe semiology (FD). Although PD patients learned more words (trials 1 to 5 on the RAVLT) than the two other groups, there was no significant difference in the total number of intrusions. However, significant differences between groups were observed for nonrelated intrusions, the proportion of PD patients (15.4%) being lower than the proportion of AD (45.5%) and FD (45.8%) patients with this type of intrusions. No other type of intrusions (same category, recurring, phonemic) significantly differentiated between the three groups. The proactive interference effect (PI), measured as the difference between first recall of list A and list B recall, was stronger in PD than in the two other groups, reflecting the strong positive correlation between total number of words recalled on the RAVLT and severity of the PI effect. Prior list intrusions (intrusions from list A while recalling list B items) were significantly more pronounced in FD than in the two other groups. Finally, free associations (series of intrusions related to one another but not to the target items) were observed almost exclusively in FD patients. These findings illustrate some qualitative differences between various neurological degenerative diseases. They also stress the marked similarities between AD and FD with regards to verbal learning.     

Updating and inhibition processes in working memory: a comparison between Alzheimer's type dementia and frontal lobe focal damage

A large debate has recently focused on the componential nature of the working-memory system (), as evidenced by functional-imaging studies and by using more sophisticated experimental paradigms. The present work aims at further disentangling the role and effects of central executive (CE) and of phonological loop (PL). It is suggested that maintaining active verbal information mostly relates to an intact PL, while the inhibition of interfering information preponderantly involves the CE. To distinguish these effects, two groups of brain damaged patients were administered with an updating task. Frontal lobe patients showed major difficulties in inhibiting interfering information, an ability requiring an involvement of the CE component. In contrast, Alzheimer's dementia patients evidenced a relative impairment in maintaining relevant information, requiring the intervention of the PL.     

Age-related quantitative and qualitative changes in decision making ability

The "frontal aging hypothesis" predicts that brain senescence affects predominantly the prefrontal regions. Preliminary evidence has recently been gathered in favour of an age-related change in a typically frontal process, i.e. decision making, using the Iowa Gambling Task (IGT), but overall findings have been conflicting. Following the traditional scoring method, coupled with a qualitative analysis, in the present study we compared IGT performance of 40 young (mean age: 27.9+/-4.7) and 40 old (mean age: 65.4+/-8.6) healthy adults and of 18 patients affected by frontal lobe dementia of mild severity (mean age: 65.1+/-7.4, mean MMSE score: 24.1+/-3.9). Quantitative findings support the notion that decision making ability declines with age; moreover, it approximates the impairment observed in executive dysfunction due to neurodegeneration. Results of the qualitative analysis did not reach statistical significance for the motivational and learning decision making components considered, but approached significance for the attentional component for elderly versus young normals, suggesting a possible decrease in the ability to maintain sustained attention during complex and prolonged tasks as the putative deficit underlying impaired decision making in normal aging.     

Loss of emotional insight in behavioral variant frontotemporal dementia or "frontal anosodiaphoria"

Loss of insight is a prominent clinical manifestation of behavioral variant frontotemporal dementia (bvFTD), but its characteristics are poorly understood. Twelve bvFTD patients were compared with 12 Alzheimer’s disease (AD) patients on a structured insight interview of cognitive insight (awareness of having a disorder) and emotional insight (concern over having a disorder). Compared to the AD patients, the bvFTD patients were less aware and less concerned about their disorder, and they had less appreciation of its effects on themselves and on others. After corrective feedback (“updating”), the bvFTD patients were just as aware of their disorder as the AD patients but remained unconcerned and unappreciative of its effects. These findings suggest that lack of insight in bvFTD is not due to “anosognosia,” or impaired cognitive and executive awareness of disease, but to “frontal anosodiaphoria,” or lack of emotional concern over having bvFTD and its impact on themselves and others.     

Clinical tests of memory in dementia, depression, and healthy aging

In Study 1, carefully screened elderly adults with primary degenerative dementia or major depression were compared to healthy aged control subjects on three tests of learning and memory: the Benton Visual Retention Test, Inglis Paired-Associate Learning Test, and the Fuld Object-Memory Evaluation (OME). The sharpest distinction in performance among the groups was observed on the OME, and discriminant equations based on this test correctly classified a high percentage (greater than or equal to 90%) of participants. Study 2 applied the classification rules derived in the first investigation to an unselected series of geropsychiatry inpatients referred for neuropsychological evaluation. There was agreement between memory test classification and general categories of clinical discharge diagnosis (organic vs. functional) for 21 of 25 patients, and with status at follow-up approximately 18 months later. Predictive value computations suggested that the OME is more accurate in confirming true dementia than in detecting dementia syndromes associated with functional disorders.     

Frontal deficits in alcoholism: an ERP study

Alcoholism is a major health problem afflicting people all over the world. Understanding the neural substrates of this addictive disorder may provide the basis for effective interventions. So-called "executive processes" play a role in cognitive functions like attention and working memory, and appear to be disrupted in alcoholism (Noel et al., 2001). Event related potentials (ERPs) provide an excellent, minimally invasive technique for exploring these neural deficits. The current study used the P300 in number sequencing task (modified version of the Petries & Milner, 1982) requiring working memory to compare a group of patients with alcoholism and frontal lobe lesions to patients with subcortical lesions and normal controls to assess the relationship of alcoholism to frontal lobe damage. The ERP paradigm was a Number Sequencing task. Electrophysiological results indicate that the frontal lesion group had significant P300 amplitude reduction and a similar trend for alcohol dependent group but not the subcortical group compared to the normal controls.     

Category and letter fluency in semantic dementia, primary progressive aphasia, and Alzheimer's disease

This study examined the impact of various degenerative dementias on access to semantic knowledge and the status of semantic representations. Patients with semantic dementia, primary progressive aphasia, and Alzheimer's disease were compared with elderly controls on tasks of category and letter fluency, with number of words generated, mean lexical frequency and errors recorded. The findings are consistent with the view that category and letter fluency rely on both common and unique cognitive processes. Fluency tasks, with the richness of data obtained, are valuable in distinguishing different dementia syndromes from one another.     

Maturation of action monitoring from adolescence to adulthood: an ERP study

This study investigated the development of the frontal lobe action-monitoring system from late childhood and adolescence to early adulthood using ERP markers of error processing. Error negativity (ERN) and correct response negativity (CRN) potentials were recorded while adolescents and adults (aged 12-22 years, n = 23) performed two forced-choice visual reaction time tasks of differing complexity. Significant age differences were seen for behavioural and ERP responses to complex (infrequent, incompatible) trials: adolescents elicited an error negativity of reduced magnitude compared with adults. Furthermore, in contrast to adults, adolescents showed a non-significant differentiation between response-locked ERP components elicited by correct (CRN) and error responses (ERN). Behaviourally, adolescents corrected fewer errors in incompatible trials, and with increasing age there was greater post-error slowing. In conclusion, the neural systems underlying action-monitoring continue to mature throughout the second decade of life, and are associated with increased efficiency for fast error detection and correction during complex tasks.     

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.     

额叶在启动效应中的作用机制：对额叶损伤病人颜色命名和词命名任务的分析

以额叶损伤病人为被试,探讨在知觉型联想启动和知觉启动中,额叶的作用及其内在机制。实验任务包括颜色命名和词命名任务,以及相应的再认任务。结果表明,额叶损伤病人在颜色命名和词命名任务中,对旧词和重组颜色词的命名时间都没有明显差别,联想启动和颜色启动效应受损,但轻度记忆损伤病人与正常对照组之间的再认成绩相似。相关分析发现联想启动和颜色启动与额叶的多项功能有中度相关。这表明,额叶参与了知觉型联想启动效应和知觉启动,并且与其抑制和注意等执行功能有关。     

Associative learning impairments in patients with frontal lobe damage

The performance of 18 frontal lobe lesion (FL) and 10 frontal lobe dementia (FLD) patients on an associative memory test was compared with the performance of their matched normal controls. The FL group was severely impaired on cued and free recall and was moderately impaired on a recognition condition. Left FL patients performed the poorest on the cued and free recall conditions. The FLD patients were moderately impaired on the free recall condition only but there was a subgroup of FLD patients with additional left temporal atrophy who appeared severely impaired on both cued and free recall. These findings indicate that both left frontal and temporal lobe damage can impair associative learning and that this impairment is more strikingly seen with free rather than cued recall.