Knowing "what for," but not "where": Dissociation between functional and contextual tool knowledge in healthy individuals and patients with dementia.

OBJECTIVE: Semantic tool knowledge underlies the ability to perform activities of daily living. Models of apraxia have emphasized the role of functional knowledge about the action performed with tools (e.g., a hammer and a mallet allow a "hammering" action), and contextual knowledge informing individuals about where to find tools in the social space (e.g., a hammer and a mallet can be found in a workshop). The goal of this study was to test whether contextual or functional knowledge, would be central in the organization of tool knowledge. It was assumed that contextual knowledge would be more salient than functional knowledge for healthy controls and that patients with dementia would show impaired contextual knowledge. METHODS: We created an original, open-ended categorization task with ambiguity, in which the same familiar tools could be matched on either contextual or functional criteria. RESULTS: In our findings, healthy controls prioritized a contextual, over a functional criterion. Patients with dementia had normal visual categorization skills (as demonstrated by an original picture categorization task), yet they made less contextual, but more functional associations than healthy controls. CONCLUSION: The findings support a dissociation between functional knowledge ("what for") on the one hand, and contextual knowledge ("where") on the other hand. While functional knowledge may be distributed across semantic and action-related factors, contextual knowledge may actually be the name of higher-order social norms applied to tool knowledge. These findings may encourage researchers to test both functional and contextual knowledge to diagnose semantic deficits and to use open-ended categorization tests.

Social cognition in adult survivors of brain tumors: studying the relationship between theory of mind and quality of life.

OBJECTIVE: The present study is the first to examine theory of mind (ToM) sequelae in a sample of adult survivors of primary brain tumors, and to investigate the assumed relationship between ToM and health-related quality of life (HRQoL). METHOD: Participants were 40 long-term adult survivors of primary brain tumors and 40 matched healthy controls. They completed ToM tests (Faux-Pas test and Advanced ToM task) and two questionnaires assessing HRQoL (36-Item Short-Form Health Survey and EORTC QLQ-C30/QLQ-BN20). Their relatives also completed an observer-rated version of the SF-36 questionnaire. RESULTS: Survivors performed worse than controls only on the Advanced ToM task. Overall, patients and caregivers reported more problems than healthy controls and their relatives regarding both global HRQoL and its social/emotional aspects. No relationship was found between ToM and HRQoL scores. CONCLUSION: Adult survivors of primary brain tumors may exhibit ToM deficits several years after treatment and report more problems on social/emotional HRQoL components. Our findings highlight the need to consider these late effects in survivors' long-term follow-up, even if the clinical involvement of ToM deficits still needs to be elucidated. The assessment of ToM deficits and their potential impact on survivors' everyday life is thoroughly discussed.

The role of cognitive estimation in understanding the mental states of others.

Previous studies have emphasized the critical role of the prefrontal cortex in cognitive estimation and theory of mind, however, none of them has questioned the possible role of cognitive estimation processes in understanding the mental states of others. In this study, we compared 30 patients with focal prefrontal cortex damage and 30 control subjects matched by gender, age, and education level on their performances on a cognitive estimation task and two tasks assessing theory of mind: the "Faux-Pas" task and the Reading the Mind in the Eyes task. The results showed that patients were significantly impaired compared with control subjects on both abilities of cognitive estimation and theory of mind. Moreover, regression analyses showed that performance on theory of mind was predicted by the scores on cognitive estimation. Finally, using voxel-based lesion analysis, we identified a partially common bilaterally distributed prefrontal network involved in both these domains centred within the ventral and dorsomedial areas with extension to the dorsolateral prefrontal cortex.

Associations between Adult Primary Brain Tumor Survivors' Behavioral Executive Functions, Health Related Quality of Life and their Caregivers' Health Related Quality : A cross-sectional study.

The present study focused on adult primary brain tumor (PBT) survivors' caregivers. The main objective was to study associations between PBT survivors' health-related quality of life (HRQOL), their behavioral executive functions (EF) and their caregivers' HRQOL. Forty PBT survivors of PBT and 37 caregivers (mostly patient's spouses 81.08%; n = 30) participated in the study. PBT survivors completed a cancer related Quality of Life (QOL) questionnaire. Caregivers completed informant rated HRQOL and behavioral EF reports relating to PBT survivors and a self-rated HRQOL questionnaire relating to themselves. Correlational and multiple regression analyses were conducted. No associations were found between caregivers' physical HRQOL and PBT survivors' HRQOL nor behavioral EF. Analyses yielded several significant correlations between caregivers' mental HRQOL and variables pertaining to PBT survivors' HRQOL and behavioral EF. Multiple regression analyses showed that caregivers' mental HRQOL is predicted by PBT survivors' mental HRQOL, global cancer-related QOL scores and global behavioral EF scores. This study provides evidence suggesting that during the survivorship phase, at an average of 3.67 (SD = 2.31) years following treatment for a PBT, caregivers mental HRQOL is linked to PBT survivors' long-term effects. These findings shed some light regarding post-cancer care for both PBT survivors and their caregivers.

Meaningless imitation in neurodegenerative diseases: Effects of body part, bimanual imitation, asymmetry, and body midline crossing.

Visuo-imitative apraxia has been consistently reported in patients with dementia, yet there have been substantial methodological differences between studies, while multiple, sometimes competing hypotheses have been put forward to explain this syndrome. Our goals were to study specific imitation deficits in groups of patients who have been selected and assigned to a group solely based on clinical criteria. We tested the effects of body part, bimanual imitation, asymmetry of the model, and body midline crossing, in patients with cortical atrophy of the temporal lobes (semantic dementia, SD), frontal-parietal networks (FPN, i.e., posterior cortical atrophy and corticobasal syndrome) or both (Alzheimer's disease, AD). Sixty-three patients and 32 healthy controls were asked to imitate 45 meaningless finger/hand, uni-/bimanual, asymmetrical/symmetrical, and crossed/uncrossed postures. SD patients had subnormal imitation scores. FPN patients showed frequent and marked deficits in most conditions, better performance with hand than finger postures (probably because of visuo-constructive deficits), and better performance with uncrossed than crossed configurations (probably because of body schema disorganization). Bimanual configurations were difficult for AD patients, not because of bimanual activity in itself, but rather because of the complexity of the model. The finding of dissociations in 34/63 cases (54%) suggests that some patients, even within the same clinical category, can have variable performance in imitation tests as a function of the abovementioned factors. Clinicians are advised to use tests with a large array of items to properly capture patients' imitation skills. This provides a new basis for future research to unpack which neurocognitive mechanisms are disrupted to cause specific patterns of impaired imitation.

Assessment of everyday executive functioning using the BRIEF in children and adolescents treated for brain tumor.

Objective: Childhood brain tumors (BTs) and their treatment often negatively affect development of executive functions. Previous studies have reported executive functions deficits, particularly through questionnaires of daily life. This study aimed to assess executive functioning in everyday life following pediatric BT, in a larger and more histologically diverse sample than previously, and to study clinical and demographic factors influencing outcome.Methods: Assessment of executive functioning using parent ratings of the Behavior Rating Inventory of Executive Function (BRIEF), in a large sample of children treated for various BT (n = 153). Clinical and demographic factors were: age at diagnostic, age at assessment, parental education level, radiation therapy.Results: Significant difficulties were found in the 3 composite indices and in the majority of the BRIEF subscales. The highest level of difficulties was observed in the Working Memory subscale. Older age at assessment and younger age at diagnosis were significantly associated with higher levels of parent-reported difficulties, particularly for metacognition.Conclusions: Parents of children treated for BT report widespread and persistent deficits in executive functions that negatively affect their everyday functioning. Including analysis of all clinical scales and composite indices allows a more comprehensive approach and enables to specify the patients' executive profile.

Effect of object substitution, spontaneous compensation and repetitive training on reaching movements in a patient with optic ataxia.

We report the case of M.B. who demonstrated severe optic ataxia with the right hand following stroke in the left hemisphere. The clinical picture may shed light on both the pathological characteristics of reaching and grasping actions, and potential rehabilitation strategies for optic ataxia. First, M.B. demonstrated a dissociation between severely impaired reaching and relatively spared grasping and tool use skills and knowledge, which confirms that grasping may be more intermingled with non-motoric cognitive mechanisms than reaching. Besides, M.B.'s reaching performance was sensitive to movement repetition. We observed a substitution effect: Reaching time decreased if M.B. repeatedly reached toward the same object but increased when object identity changed. This may imply that not only object localization but also object identity, is integrated into movement programming in reach-to-grasp tasks. Second, studying M.B.'s spontaneous compensation strategies ascertained that the mere repetition of reaching movements had a positive effect, to the point M.B. almost recovered to normal level after an intensive one-day repetitive training session. This case study seems to provide one of the first examples of optic ataxia rehabilitation. Reaching skills can be trained by repetitive training even two years post-stroke and despite the presence of visuo-imitative apraxia.

Executive Functions in Children and Adolescents with Turner Syndrome: A Systematic Review and Meta-Analysis.

Turner syndrome (TS) is a genetic disorder, affecting 1/2500 to 1/3000 live female births, induced by partial or total deletion of one X chromosome. The neurocognitive profile of girls with TS is characterized by a normal Verbal IQ and weaknesses in visual-spatial, mathematics, and social cognitive domains. Executive functions (EFs) impairments have also been reported in these young patients. However, methodological differences across studies do not allow determination of which EFs are impaired and what is the magnitude of these impairments. The aim of this review was to clarify the EF profile of children and adolescents with TS. Sixteen samples, from thirteen studies, were included in the current meta-analysis. EFs measures used in these studies were classified into working memory, inhibitory control, cognitive flexibility, or higher-order EFs tasks in accordance with Diamond's model, Annual Review of Psychology, 64, 135-168 (2013). Results confirmed that girls with TS had significant executive impairments with effect sizes varying from small (inhibitory control) to medium (cognitive flexibility) and large (working memory, higher-order EFs). Analyses by task revealed that cognitive inhibition may be more impaired than the other inhibitory control abilities. Heterogeneity across cognitive flexibility measures was also highlighted. Between-sample heterogeneity was observed for three tasks and the impact of participants' characteristics on EFs was discussed. This meta-analysis confirms the necessity to assess, in patients living with TS, each EF by combining both visual and verbal tasks. Results also underline that, when studying girls with TS' executive profile, it is important to explore the impact of moderator variables, such as IQ, parental socio-economic status, TS karyotype, psychiatric comorbidities, and hormonal treatment status.

Frontal versus dysexecutive syndromes: relevance of an interactionist approach in a case series of patients with prefrontal lobe damage.

The concepts of "frontal" and "dysexecutive" syndromes are still a matter of debate in the literature. These terms are often used interchangeably but can be distinguished when considering specific frontal behavioural deficits which occur during social interaction. Despite being of interest for the clinical assessment and care management of patients with anterior brain damage, few studies have tried to disentangle the specificity of each syndrome. We report the case of eight patients with frontal lobe damage who were assigned to one of two groups based on whether or not they showed a dysexecutive syndrome. The nondysexecutive group differed from the dysexecutive group in showing environmental dependency phenomena, behavioural disorders triggered by social interaction. By adopting an interactionist perspective, this pilot study contributes to defining more precisely the distinction between "frontal" and "dysexecutive" syndromes. The discussion focuses on the potential interest of the interactionist approach in designing appropriate methodologies of assessment and rehabilitation of patients with frontal lobe syndrome.

Rethinking the Cognitive Mechanisms Underlying Pantomime of Tool Use: Evidence from Alzheimer's Disease and Semantic Dementia.

OBJECTIVES: Pantomiming the use of familiar tools is a central test in the assessment of apraxia. However, surprisingly, the nature of the underlying cognitive mechanisms remains an unresolved issue. The aim of this study is to shed a new light on this issue by exploring the role of functional, mechanical, and manipulation knowledge in patients with Alzheimer's disease and semantic dementia and apraxia of tool use. METHODS: We performed multiple regression analyses with the global performance and the nature of errors (i.e., production and conception) made during a pantomime of tool use task in patients and control participants as dependent variables and tasks investigating functional, mechanical, and manipulation knowledge as predictors. RESULTS: We found that mechanical problem solving, assessing mechanical knowledge, was a good predictor of the global performance of pantomime of tool use. We also found that occurrence of conception errors was robustly predicted by the task assessing functional knowledge whereas that of production errors was not explained by only one predictor. CONCLUSIONS: Our results suggest that both functional and mechanical knowledge are important to pantomime the use of tools. To our knowledge, this is the first demonstration that mechanical knowledge plays a role in pantomime of tool use. Although impairment in pantomime of tool use tasks (i.e., apraxia) is widely explained by the disruption of manipulation knowledge, we propose that pantomime of tool use is a complex problem-solving task. (JINS, 2017, 23, 128-138).

Contribution of different regions of the prefrontal cortex and lesion laterality to deficit of decision-making on the Iowa Gambling Task.

Few studies have examined the contribution of different sub-regions of the prefrontal cortex and lesion laterality to decision-making abilities. In addition, there are inconsistent findings about the role of ventromedial and dorsolateral lesions in decision-making deficit. In this study, decision-making processes are investigated following different damaged areas of the prefrontal cortex. We paid particular attention to the contribution of laterality, lesion location and lesion volume in decision-making deficit. Twenty-seven patients with discrete ventromedial lesions, dorsolateral lesions or extended-frontal lesions were compared with normal subjects on the Iowa Gambling Task (IGT). Our results showed that all frontal subgroups were impaired on the IGT in comparison with normal subjects. We noted also that IGT performance did not vary systematically based on lesion laterality or location. More precisely, our lesion analysis revealed that decision-making processes depend on a large cerebral network, including both ventromedial and dorsolateral areas of the prefrontal cortex. Consistent with past findings, our results support the claim that IGT deficit is not solitarily associated with ventromedial prefrontal cortex lesions.

Ecological Assessment of Everyday Executive Functioning at Home and at School Following Childhood Traumatic Brain Injury Using the BRIEF Questionnaire.

OBJECTIVES: To describe dysexecutive symptoms in children with traumatic brain injury (TBI) using the Behavior Rating Inventory of Executive Function (BRIEF); to compare parent- and teacher-ratings, to analyze the differential impairment in the BRIEF subscales, and factors influencing outcome. PARTICIPANTS: Children aged 5 to 18 years 11 months, referred to a rehabilitation department following TBI. OUTCOME MEASURES: Parent- and teacher reports of the BRIEF. RESULTS: A total of 194 patients participated in the study: mild (n = 13), moderate (n = 12), severe (n = 169); mean 4.92 (standard deviation = 3.94) years post-injury. According to parent ratings (n = 193), all BRIEF subscales and indices were significantly elevated (23.8%-48% in the clinical range). The Working Memory subscale score was significantly higher than all other subscales. Results of teacher ratings (n = 28) indicated similar significantly elevated scores in all subscales (39.3%-57.2% in the clinical range). No significant difference was found between parent and teacher ratings, which were significantly correlated. Regression analyses indicated that, in children with severe TBI, parental BRIEF overall and metacognition indices were significantly predicted by younger age at injury and older age at assessment, whereas no significant predictor of behavioral regulation index was identified. DISCUSSION AND CONCLUSION: This study highlights significant executive dysfunction in everyday life several years after childhood TBI, evident in home and school environments.

Imitation and matching of meaningless gestures: distinct involvement from motor and visual imagery.

The aim of the present study was to understand the underlying cognitive processes of imitation and matching of meaningless gestures. Neuropsychological evidence obtained in brain damaged patients, has shown that distinct cognitive processes supported imitation and matching of meaningless gestures. Left-brain damaged (LBD) patients failed to imitate while right-brain damaged (RBD) patients failed to match meaningless gestures. Moreover, other studies with brain damaged patients showed that LBD patients were impaired in motor imagery while RBD patients were impaired in visual imagery. Thus, we hypothesize that imitation of meaningless gestures might rely on motor imagery, whereas matching of meaningless gestures might be based on visual imagery. In a first experiment, using a correlational design, we demonstrated that posture imitation relies on motor imagery but not on visual imagery (Experiment 1a) and that posture matching relies on visual imagery but not on motor imagery (Experiment 1b). In a second experiment, by manipulating directly the body posture of the participants, we demonstrated that such manipulation evokes a difference only in imitation task but not in matching task. In conclusion, the present study provides direct evidence that the way we imitate or we have to compare postures depends on motor imagery or visual imagery, respectively. Our results are discussed in the light of recent findings about underlying mechanisms of meaningful and meaningless gestures.

Executive Functions Deficits After Severe Traumatic Brain Injury: The GREFEX Study.

OBJECTIVE: To assess the sensitivity of traditional neuropsychological tests and of a behavioral inventory of executive disorders in a large sample of patients with chronic severe traumatic brain injury. METHODS: A total of 112 patients were compared with 780 healthy controls from a larger database. The GREFEX battery included 7 widely used tests and the Behavioral Dysexecutive Syndrome Inventory (proxy rating). A previously described statistical methodology was used, controlling for age, education, and gender. Summary scores were computed and performance was dichotomized on the basis of 5th percentile cutoffs from controls' z scores. RESULTS: The frequency of cognitive impairment was high (55.4%) but lower than that of behavioral changes (81.5%). Double dissociations were observed between cognitive and behavioral assessments. Behavioral changes exhibited larger effect-sizes as compared with cognitive impairments. Logistic regression analysis showed that 3 cognitive tests (verbal fluency, Stroop reading, and Trail Making Test-B) and 3 behavior z scores (hypoactivity, anticipation, and hyperactivity) best discriminated patients from controls. CONCLUSION: Behavioral changes were more frequent and severe than cognitive deficits, at least as assessed with traditional testing. The present results also suggest that a shortened battery may provide a rapid screening method with reasonable sensitivity to detect deficits of executive functions in patients with severe traumatic brain injury.

Detecting everyday action deficits in Alzheimer's disease using a nonimmersive virtual reality kitchen.

Alzheimer's disease (AD) causes impairments affecting instrumental activities of daily living (IADL). Transdisciplinary research in neuropsychology and virtual reality has fostered the development of ecologically valid virtual tools for the assessment of IADL, using simulations of real life activities. Few studies have examined the benefits of this approach in AD patients. Our aim was to examine the utility of a non-immersive virtual coffee task (NI-VCT) for assessment of IADL in these patients. We focus on the assessment results obtained from a group of 24 AD patients on a task designed to assess their ability to prepare a virtual cup of coffee, using a virtual coffee machine. We compared performance on the virtual task to an identical daily living task involving the actual preparation of a cup of coffee, as well as to global cognitive, executive, and caregiver-reported IADL functioning. Relative to 32 comparable, healthy elderly (HE) controls, AD patients performed worse than HE controls on all tasks. Correlation analyses revealed that NI-VCT measures were related to all other neuropsychological measures. Moreover, regression analyses demonstrated that performance on the NI-VCT predicted actual task performance and caregiver-reported IADL functioning. Our results provide initial support for the utility of our virtual kitchen for assessment of IADL in AD patients.

Pragmatic language comprehension: Role of theory of mind, executive functions, and the prefrontal cortex.

The specific contribution of focal damage of the prefrontal cortex and the cognitive mechanisms accounting for communicative-pragmatic disorders remains unclear. The objective of the current study was to investigate the impact of focal prefrontal cortex damage on the ability to understand indirect speech or hints and to identify the prefrontal neural mechanisms involved. We also examined the underlying cognitive mechanisms of disorders of indirect speech understanding particularly theory of mind and executive functions. Thirty patients with focal prefrontal cortex damage and 30 control subjects were compared on their performances on the Hinting task assessing pragmatic language skills, the "Faux-Pas" task and the Reading the Mind in the Eyes task assessing Theory of Mind and a battery of executive tasks. Patients were significantly impaired compared with control subjects on all these abilities. Both deficits of executive functions and theory of mind were able to predict impaired ability of patients in understanding non-literal meanings on the Hinting task. Finally, using voxel-based lesion analysis we identified a partially shared neural prefrontal network involved in all these abilities centered on the dorsomedial and ventral regions of the prefrontal cortex.

Apraxia and Alzheimer's disease: review and perspectives.

Apraxia is one of the cognitive deficits that characterizes Alzheimer's disease. Despite its prevalence and relevance to diagnosing Alzheimer's disease, this topic has received little attention and is without comprehensive review. The review herein is aimed to fill this gap by first presenting an overview of the impairment caused in different clinical situations: pantomime of tool use, single tool use, real tool use, mechanical problem solving, function and manipulation knowledge tasks, and symbolic/meaningless gestures. On the basis of these results, we then propose alternative interpretations regarding the nature of the underlying mechanisms impaired by the disease. Also presented are principal methodological issues precluding firm conclusions from being drawn.

Role of the prefrontal cortex and executive functions in basic emotions recognition: evidence from patients with focal damage to the prefrontal cortex.

Few studies have examined the specific contribution of focal damage of the prefrontal cortex and executive dysfunction to emotion recognition deficits, with results reporting controversial findings. This study investigated the performance of 30 patients with prefrontal cortex damage and 30 matched controls on a battery of executive measures assessing processes of inhibition, flexibility, and planning and a task of emotion recognition with also a particular attention to the examination of the association between these domains. The results showed that compared with control participants, patients with prefrontal cortex damage were impaired in recognizing the three negative emotions of fear, sadness, and anger and were also impaired on all executive measures. Moreover, by examining the association between both these domains, using correlation and regression analyses, we noted that impaired performance in recognizing emotions of fear, sadness, and anger was predicted by impaired performances on the measures of inhibition and flexibility or "set-shifting" suggesting that the ability to recognize emotions could be at least to some extent cognitively mediated. Finally, using a voxel-based lesion technique, we identified a partially common prefrontal network underlying deficits on executive functions and emotions recognition centered on the ventral and medial parts of the prefrontal cortex, reflecting beyond the neural network involved in recognizing negative emotions per se that of the cognitive processes elicited by this emotion task.

Sensory Integration Deficits in Neurodegenerative Diseases: Implications for Apraxia.

OBJECTIVE: Apraxia is the inability to perform voluntary, skilled movements following brain lesions, in the absence of sensory integration deficits. Yet, patients with neurodegenerative diseases (ND) may have sensory integration deficits, so we tested the associations and dissociations between apraxia and sensory integration. METHODS: A total of 44 patients with ND and 20 healthy controls underwent extensive testing of sensory integration (i.e., localization of tactile, visual, and proprioceptive stimuli; agraphesthesia; astereognosis) and apraxia (i.e., finger dexterity, imitation, tool use). RESULTS: The results showed (i) that patients with Alzheimer's disease, corticobasal syndrome, or posterior cortical atrophy were impaired on both dimensions; (ii) An association between both dimensions; (iii) that when sensory integration was controlled for, the frequency of apraxia decreased dramatically in some clinical subgroups. CONCLUSION: In a non-negligible portion of patients, the hypothesis of a disruption of sensory integration can be more parsimonious than the hypothesis of apraxia in case of impaired skilled gestures. Clinicians and researchers are advised to integrate sensory integration measures along with their evaluation of apraxia.

Assessing the construct validity of a theory of mind battery adapted to Tunisian school-aged children.

Background: Theory of mind (ToM) refers to the ability to understand others' states of mind, desires, emotions, beliefs, and intentions to predict the content of their mental representations. Two major dimensions within ToM have been studied. The first is the type of inferred mental state, which can be cognitive or affective. The second comprises the types of processes involved according to their degree of complexity (first- and second-order false belief and advanced ToM). ToM acquisition is fundamental-a key component in the development of everyday human social interactions. ToM deficits have been reported in various neurodevelopmental disorders through various tools assessing disparate facets of social cognition. Nevertheless, Tunisian practitioners and researchers lack a linguistically and culturally appropriate psychometric tool for ToM assessment among school-aged children. Objective: To assess the construct validity of a translated and adapted French ToM Battery for Arabic-speaking Tunisian school-aged children. Methods: The focal ToM Battery was designed with neuropsychological and neurodevelopmental theory and composed of 10 subtests distributed evenly in three parts: Pre-conceptual, cognitive, and affective ToM. Translated and adapted to the Tunisian sociocultural context, this ToM battery was individually administered to 179 neurotypical Tunisian children (90 girls and 89 boys) aged 7-12 years. Results: After controlling for the age effect, construct validity was empirically confirmed on two dimensions (cognitive and affective) via structural equation modeling (SEM) analysis, demonstrating that this solution has a good fit. The results confirmed that the age affected differentially the performance obtained on ToM tasks based on the two components of the battery. Conclusion: Our findings confirm that the Tunisian version of the ToM Battery has robust construct validity for the assessment of cognitive and affective ToM in Tunisian school-aged children; hence, it could be adopted in clinical and research settings.