Andrea Slachevsky

The FAB: A frontal assessment battery at bedside

&NA; Objective: To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions. Methods The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10 minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe dysfunction (PD, n = 24; multiple system atrophy, n = 6; corticobasal degeneration, n = 21; progressive supranuclear palsy, n = 47; frontotemporal dementia, n = 23). Results The Frontal Assessment Battery scores correlated with the Mattis Dementia Rating Scale scores (rho = 0.82, p < 0.01) and with the number of criteria (rho = 0.77, p < 0.01) and perseverative errors (rho = 0.68, p < 0.01) of the Wisconsin Card Sorting Test. These variables accounted for 79% of the variance in a stepwise multiple regression, whereas age or Mini-Mental State Examination scores had no significant influence. There was good interrater reliability (&kgr; = 0.87, p < 0.001), internal consistency (Cronbachs coefficient alpha = 0.78), and discriminant validity (89.1% of cases correctly identified in a discriminant analysis of patients and controls). Conclusion The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.

Causal role of prefrontal cortex in the threshold for access to consciousness

What neural mechanisms support our conscious perception of briefly presented stimuli? Some theories of conscious access postulate a key role of top-down amplification loops involving prefrontal cortex (PFC). To test this issue, we measured the visual backward masking threshold in patients with focal prefrontal lesions, using both objective and subjective measures while controlling for putative attention deficits. In all conditions of temporal or spatial attention cueing, the threshold for access to consciousness was systematically shifted in patients, particular after a lesion of the left anterior PFC. The deficit affected subjective reports more than objective performance, and objective performance conditioned on subjective visibility was essentially normal. We conclude that PFC makes a causal contribution to conscious visual perception of masked stimuli, and outline a dual-route signal detection theory of objective and subjective decision making.

Preserved Adjustment but Impaired Awareness in a Sensory–Motor Conflict following Prefrontal Lesions

Control of action occurs at different stagesof the executive process, in particular at those of sensory-motor integration and conscious monitoring. The aim of this study was to determine the implication of the prefrontal cortex in the control of action. For that purpose, we compared the performance of 15 patients with frontal lobe lesions and 15 matched controls on an experimental paradigm generating a conflict between the action planned and the sensory-motor feedback. Subjects had to trace a sagittal line witha stylus on a graphic tablet. The hand was hidden by a mirror on which the traced line, processed by a computer, was projected. Without informing the subjects, the line traced was modified by introducing a bias to the right, which increased progressively from 2 to 42. To succeed the task, subjects had to modify their motor program and deviate their hand in the opposite direction. The sensory-motor adjustment to the bias was evaluated by the surface between the line traced and the ideal line to compensate for the deviation. The awareness of the conflict was measured by the angle of the bias at which subjects expressed the feeling that the line they traced was not the same as the line they saw. The deviation was similarly compensated for by patients and controls until24. Then 14 controls but only3 patients were aware of a conflict. After that, the variability of performance increased significantly for the unaware patients. These results suggest that the prefrontal cortex is required at the level of conscious monitoring of actions, but not at the level of sensory-motor integration.

Applause sign helps to discriminate PSP from FTD and PD

The “applause sign” is a simple test of motor control that helps to differentiate PSP from frontal or striatofrontal degenerative diseases. It was found in 0/39 controls, 0 of 24 patients with frontotemporal dementia (FTD), 0 of 17 patients with Parkinson disease (PD), and 30/42 patients with progressive supranuclear palsy (PSP). It discriminated PSP from FTD (p < 0.001) and PD (p < 0.00). The “three clap test” correctly identified 81.8% of the patients in the comparison PSP and FTD and 75% of the patients in the comparison of PSP and PD.

Executive Functioning in Schizophrenia

The executive function (EF) is a set of abilities, which allows us to invoke voluntary control of our behavioral responses. These functions enable human beings to develop and carry out plans, make up analogies, obey social rules, solve problems, adapt to unexpected circumstances, do many tasks simultaneously, and locate episodes in time and place. EF includes divided attention and sustained attention, working memory (WM), set-shifting, flexibility, planning, and the regulation of goal directed behavior and can be defined as a brain function underlying the human faculty to act or think not only in reaction to external events but also in relation with internal goals and states. EF is mostly associated with dorsolateral prefrontal cortex (PFC). Besides EF, PFC is involved in self-regulation of behavior, i.e., the ability to regulate behavior according to internal goals and constraints, particularly in less structured situations. Self-regulation of behavior is subtended by ventral medial/orbital PFC. Impairment of EF is one of the most commonly observed deficits in schizophrenia through the various disease stages. Impairment in tasks measuring conceptualization, planning, cognitive flexibility, verbal fluency, ability to solve complex problems, and WM occur in schizophrenia. Disorders detected by executive tests are consistent with evidence from functional neuroimaging, which have shown PFC dysfunction in patients while performing these kinds of tasks. Schizophrenics also exhibit deficit in odor identifying, decision-making, and self-regulation of behavior suggesting dysfunction of the orbital PFC. However, impairment in executive tests is explained by dysfunction of prefronto-striato-thalamic, prefronto-parietal, and prefronto-temporal neural networks mainly. Disorders in EFs may be considered central facts with respect to schizophrenia and it has been suggested that negative symptoms may be explained by that executive dysfunction.

Perception of self-generated action in schizophrenia

Introduction. Self-generated actions involve central processes of sensorimotor integration that continuously monitor sensory inputs to ensure that motor outputs are congruent with our intentions. This mechanism works automatically in normal conditions but becomes conscious whenever a mismatch happens during the execution of action between expected and current sensorimotor reafferences. It is now admitted in the literature that sensorimotor processes as well as the ability to predict the consequences of our own actions imply the existence of a forward model of action, which is based on efference copies. Recently, it has been proposed that positive symptoms expressed by schizophrenic patients, such as delusions of control or thought insertions, arise because of a deficiency in this forward model, and more particularly, because of a lack of awareness of certain aspects of motor control derived from such an internal model. Method. To test further this hypothesis, 19 schizophrenic patients (10 with and 9 without Schneiderian symptoms) and 19 control subjects performed a visuo-motor conflict task and had verbally to report the felt position of their hand at the end of each trial. Results. Under this experimental procedure, schizophrenic patients - whatever their clinical phenotype - failed to switch to a conscious representation of their hand movements, and then consequently to maintain their level of performance for the sensorimotor adjustment in comparison with controls. Conclusion. Our findings suggest two facts. First, that a functional monitoring of action, based on a forward

Testing the model of caudo-rostral organization of cognitive control in the human with frontal lesions.

The cascade model of cognitive control, mostly relying on functional neuroimaging studies, stipulates that the lateral frontal cortex (LFC) is organized as a cascade of executive processes involving three levels of cognitive control, implemented in distinct LFC areas from the premotor to the anterior prefrontal regions. The present experiment tested this model in patients with LFC lesions and studied the hierarchy of executive functions along the caudo-rostral axis, i.e. the respective roles of the different LFC areas in the control of behavior. Voxel-based lesion-symptom mapping and region of interest group analyses were conducted in 32 patients with focal LFC lesions who performed cognitive tasks assessing the cascade model. We first showed that three different LFC areas along the caudo-rostral axis subserved three distinct control levels, whose integrity is necessary for adaptive behavior. Second, we found that prefrontal cognitive control has an asymmetric organization: higher control processes involving more anterior prefrontal regions rely on the integrity of lower control processes in more posterior regions, while lower control processes can operate irrespective of the integrity of higher control processes. Altogether, these findings support a caudo-rostral cascade of executive processes from premotor to anterior prefrontal regions.

The prefrontal cortex and conscious monitoring of action An experimental study

To investigate the role of the prefrontal cortex in conscious monitoring, we used an experimental paradigm generating a conflict between the action planned and the sensory-motor feedback. We analyzed the acquisition of explicit knowledge of the strategy for resolving the conflict and its influence on motor adaptation. Twenty patients with frontal lobe lesions and 18 controls had to trace a sagittal line with a stylus on a graphics tablet. A mirror on which the traced line, processed by a computer, was projected hid the hand. A mask limited visual feedback to the last third of the trajectory. Without informing the subjects, the line traced was modified by introducing a bias of 24 degrees to the right. To succeed in the task, subjects had to modify their motor program and to deviate their trajectory in the opposite direction. Conscious elaboration of the strategy was evaluated by the number of trials needed to explicitly report the required deviation. Three groups of patients were distinguished: (1). with normal explicit strategy; (2). with delayed explicit strategy, and (3). without explicit strategy at the last trial. They significantly differed by the severity of the dysexecutive syndrome, particularly of environmental adherence. Motor adaptation was evaluated by the area between the line traced and the ideal line to compensate for the deviation. In patients with normal elaboration of the strategy, motor control was similar to that of controls, but it was severely disturbed in the other two groups. These results suggest the involvement of the prefrontal cortex in conscious motor monitoring.

Human platelets tau: a potential peripheral marker for Alzheimer's disease.

Platelets are a major peripheral reservoir of the amyloid-β protein precursor, so they have been considered as a potential biological marker of Alzheimers disease (AD). Here, it is demonstrated that tau protein is also present in platelets and that the levels of oligomeric species of this protein could serve as a novel and reliable biological marker for AD. Blood samples were obtained from 15 AD patients and 10 paired-age controls and platelets were separated via differential centrifugation. The purity of platelets was determined by flow cytometry and microscopy and the presence of tau was determined by immunofluorescence and immunoblots with tau specific antibodies. Immunofuorescence and immunoblot patterns of platelets were positive for tau. Immunoblots also showed the presence of high molecular weight (HMW) variants of tau that appeared to correspond to oligomeric forms of the protein. The ratio of HMW tau respect to tau monomeric species was significantly higher in AD patients than controls. The present is the first description of the presence of tau in platelets. The analysis of different tau fractions in platelets could serve as a new biological marker for AD.

Comparing Moral Judgments of Patients With Frontotemporal Dementia and Frontal Stroke

IMPORTANCE Several clinical reports have stated that patients with prefrontal lesions or patients with the behavioral variant of frontotemporal dementia share social cognition impairments. Moral reasoning is impaired in both conditions but there have been few investigations that directly compare this domain in the 2 groups. OBSERVATIONS This work compared the moral judgments of these patient groups using a task designed to disentangle the contributions of intentions and outcomes in moral judgment. For both disorders, patients judged scenarios where the protagonists believed that they would cause harm but did not as being more permissible than the control group. Moreover, patients with frontotemporal dementia judged harmful outcomes in the absence of harmful intentions as less permissible than the control participants. There were no differences between the 2 conditions. CONCLUSIONS AND RELEVANCE Both disorders involved impairments in integrating intention and outcome information for moral judgment. This study was the first, to our knowledge, to directly compare a social cognition domain in 2 frontal pathologies with different etiology. Our results highlighted the importance of comparing patients with vascular lesions and patients with neurodegenerative diseases.