Incidental Verbal Semantic Processing Recruits the Fronto-temporal Semantic Control Network.

The frontoparietal semantic network, encompassing the inferior frontal gyrus and the posterior middle temporal cortex, is considered to be involved in semantic control processes. The explicit versus implicit nature of these control processes remains however poorly understood. The present study examined this question by assessing regional brain responses to the semantic attributes of an unattended stream of auditory words while participants' top-down attentional control processes were absorbed by a demanding visual search task. Response selectivity to semantic aspects of verbal stimuli was assessed via a functional magnetic resonance imaging response adaptation paradigm. We observed that implicit semantic processing of an unattended verbal stream recruited not only unimodal and amodal cortices in posterior supporting semantic knowledge areas, but also inferior frontal and posterior middle temporal areas considered to be part of the semantic control network. These results indicate that frontotemporal semantic networks support incidental semantic (control) processes.

[The effect of normal and pathological aging on cognition]. / Les effets du vieillissement normal et pathologique sur la cognition.

Cognitive deficits in the executive and memory domains are observed in normal aging and Alzheimer's disease (AD). These deficits are associated with changes at the brain activity level. However, a series of factors are prone to delay the occurrence of cognitive deficits, such as mental stimulation or physical activity. Similarly, cognitive rehabilitation allows improving the daily life functioning of patients with AD. The identification of factors and techniques that contribute to maintain cognitive efficiency and/or counteract the effects of AD will allow optimizing quality of life of older people.

The Complex Interplay Between Trait Fatigue and Cognition in Multiple Sclerosis.

Cognitive impairments are frequent in patients with Multiple Sclerosis (MS). Yet, the influence of MS-related symptoms on cognitive status is not clear. Studies investigating the impact of trait fatigue along with anxio-depressive symptoms on cognition are seldom, and even less considered fatigue as multidimensional. Moreover, these studies provided conflicting results. Twenty-nine MS patients and 28 healthy controls, matched on age, gender and education underwent a full comprehensive neuropsychological assessment. Anxio-depressive and fatigue symptoms were assessed using the HAD scale and the MFIS, respectively. Six composite scores were derived from the neuropsychological assessment, reflecting the cognitive domains of working memory, verbal and visual learning, executive functions, attention and processing speed. Stepwise regression analyses were conducted in each group to investigate if trait cognitive and physical fatigue, depression and anxiety are relevant predictors of performance in each cognitive domain. In order to control for disease progression, patient's EDSS score was also entered as predictor variable. In the MS group, trait physical fatigue was the only significant predictor of working memory score. Cognitive fatigue was a predictor for executive functioning performance and for processing speed (as well as EDSS score for processing speed). In the healthy controls group, only an association between executive functioning and depression was observed. Fatigue predicted cognition in MS patients only, beyond anxio-depressive symptoms and disease progression. Considering fatigue as a multidimensional symptom is paramount to better understand its association with cognition, as physical and cognitive fatigue are predictors of different cognitive processes.

A comparison of unawareness in frontotemporal dementia and Alzheimer's disease.

BACKGROUND: Loss of insight is a core diagnostic feature of frontotemporal dementia (FTD) and anosognosia is frequently reported in Alzheimer's disease (AD). AIM: To compare unawareness (anosognosia) for different symptoms, measured with a discrepancy score between patient's and caregiver's assessment, in AD and FTD. METHOD: In a prospective, multi-centre study, 123 patients with probable AD, selected according to the NINCDS-ADRDA procedure, were matched for age, sex, education, disease duration and dementia severity to patients with FTD (n = 41), selected according to international consensus criteria. A research complaint questionnaire was used to obtained patient's and caregiver's assessment concerning neuropsychological and behavioural symptoms. Data were compared in each group and between groups. Unawareness (measured by discrepancy scores) was compared between patients with AD and FTD. RESULTS: The caregivers generally assessed symptoms more severely than did patients, but both patient groups reported changes in affect (depressive mood or irritability) as their caregivers did. Unawareness was greater in patients with FTD than in patients with AD for language and executive difficulties, and for changes in behaviour and daily activities. CONCLUSION: The main finding is that unawareness was observed in both patients with FTD and patients with AD for most clinical domains. However, qualitative and quantitative differences showed that lack of awareness was greater in patients with FTD.

[Brain imaging of reflection on self]. / Imagerie cérébrale de la réflexion sur soi.

Precise brain regions are activated when a subject gives a judgment on himself. Those are the medial parietal cortex, essentially related to episodic memory processing, and the ventromedial prefrontal cortex, recruited for evaluating the personal valence of an information. These regions are not activated in Alzheimer's disease. The decrease of awareness for own deficits in a patient with Alzheimer's disease would depend on a reduction of episodic memory capacities and a worsening of judgment for self significance.

Is Alzheimer's disease a disconnection syndrome? Evidence from a crossmodal audio-visual illusory experiment.

In Alzheimer's disease (AD), loss of connectivity in the patient's brain has been evidenced by a range of electrophysiological and neuroimaging studies. However, few neuropsychological research projects have sought to interpret the cognitive modifications following the appearance of AD in terms of a disconnection syndrome. In this paper, we sought to investigate brain connectivity in AD via the study of a crossmodal effect. More precisely, we examined the integration of auditory and visual speech information (the McGurk effect) in AD patients and matched control subjects. Our results revealed impaired crossmodal integration during speech perception in AD, which was not associated with disturbances in the separate processing of auditory and visual speech stimuli. In conclusion, our data suggest the occurrence of a specific, audio-visual integration deficit in AD, which might be the consequence of a connectivity breakdown and corroborate the observation from other studies of crossmodal deficits between the auditory and visual modalities in this population.

Exploration of the neural substrates of executive functioning by functional neuroimaging.

This review presents neuroimaging studies that have explored the cerebral substrates of executive functioning. These studies have demonstrated that different executive functions not only recruit various frontal areas but also depend upon posterior (mainly parietal) regions. These results are in accordance with the hypothesis that executive functioning relies on a distributed cerebral network that is not restricted to anterior cerebral areas. However, there exists an important heterogeneity in the cerebral areas associated with these different processes, and also between different tasks assessing the same process. Since these discrepant results could be due to the paradigms used (subtraction designs), recent results obtained with conjunction and interaction analyses are presented, which confirm the role of parietal areas in executive functioning and also demonstrate the existence of some specificity in the neural substrates of the executive processes of updating, shifting and inhibition. Finally, functional magnetic resonance imaging studies show that the activity in cerebral areas involved in executive tasks can be transient or sustained. Consequently, to better characterize the functional role of areas associated with executive functioning, it is important to take into account not only the localization of cerebral activity but also the temporal pattern of this activity.

Cerebral metabolic correlates of four dementia scales in Alzheimer's disease.

Different scales can be used to evaluate dementia severity in Alzheimer's disease (AD). They do assess different cognitive or functional abilities, but their global scores are frequently in mutual correlation. Functional imaging provides an objective method for the staging of dementia severity. Positron emission tomography was used to assess the relationship between brain metabolism and four dementia scales that reflect a patient's global cognitive abilities (mini mental state), caregiver's evaluation of cognitive impairment (newly designed scale), daily living functioning (instrumental activities of daily living) and global dementia (clinical dementia rating). We wondered whether different clinical dementia scales would be related to severity of metabolic impairment in the same brain regions, and might reflect impairment of common cognitive processes. 225 patients with probable AD were recruited in a prospective multicentre European study. All clinical scales were related to brain metabolism in associative temporal, parietal or frontal areas. A factorial analysis demonstrated that all scales could be classified in a single factor. That factor was highly correlated to decrease of cerebral activity in bilateral parietal and temporal cortices, precuneus, and left middle frontal gyrus. This finding suggests that global scores for all scales provided similar information on the neural substrate of dementia severity. Capitalizing on the neuroimaging literature, dementia severity reflected by reduced metabolism in posterior and frontal associative areas in AD might be related to a decrease of controlled processes.

Functional imaging of executive functions.

Executive functioning refers to cognitive processes that facilitate our adaptation to new or complex situations when action routines are not efficient. Neuropsychological studies in brain-damaged patients suggested that executive functions were predominantly dependent on prefrontal regions. However, prefrontal lesions frequently occurred in a context of more widespread brain involvement, and a dysexecutive syndrome was described in posterior cortical dementia of the Alzheimer type. Functional imaging can precisely identify brain networks involved in executive functioning. We discuss functional imaging studies that show both frontal and posterior activation during executive tasks and bring information concerning unity and diversity in executive processes.

Brain Metabolic Dysfunction in Capgras Delusion During Alzheimer's Disease: A Positron Emission Tomography Study.

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer's disease (AD) and Capgras syndrome was compared with those of 24-healthy elderly participants and 26 patients with AD without delusional syndrome. Comparing the healthy group with the AD group, the patient with AD had significant hypometabolism in frontal and posterior midline structures. In the light of current neural models of face perception, our patients with Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex.

Phonological loop and central executive functioning in Alzheimer's disease.

The phonological loop and central executive functioning were examined in patients with Alzheimer's disease (AD) and in normal elderly subjects. AD patients showed abnormal functioning of the phonological loop and decreased performance on tasks assessing the central executive. However, when AD patients were separated into two groups on the basis of their span level, both groups showed deficits of the central executive but only patients with the lower span level presented a dysfunction of the phonological loop as well as impaired performance in tasks of phonological discrimination, articulation rate and speed of processing. These results are interpreted in terms of progression of the disease, with high-span level patients being less severely demented and displaying deficits only in higher-level cognitive functions (such as manipulation of information stored in working memory) whereas patients with a low span level have impairments encompassing a series of more basic processes.

Effects of incidental and intentional feature binding on recognition: a behavioural and PET activation study.

Using Positron Emission Tomography (PET), we investigated cerebral regions associated with the episodic recognition of words alone and words bound to contextual colours. Two modes of colour encoding were tested: incidental and intentional word-to-colour binding. Word-only recognition was associated with brain activation in a lexico-semantic left middle temporal region and in the cerebellum following an incidental colour encoding, and with brain activation in the left posterior middle frontal gyrus, right anterior cingulate and right inferior frontal gyrus following an intentional encoding. Recognition of bound features was associated with activation in left prefrontal and superior parietal regions following an incidental colour encoding, and with preferential right prefrontal cortex activation following an intentional colour encoding. Our results are in line with the hypothesis of a parietal involvement in context processing, and prefrontal areas in monitoring retrieval processes. Our results also support the hypothesis of a 'cortical asymmetry for reflective activity' (CARA).

Regional brain activity during tasks devoted to the central executive of working memory.

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.

Executive dysfunction in Alzheimer's disease.

Executive functioning was examined in 20 patients with Alzheimer's disease (AD) and 20 normal elderly subjects. The results showed that AD patients present lower performance compared to control subjects in all executive tasks, confirming that some executive deficits may be present in the first stages of the disease. A factorial analysis suggested that these deficits can be related to two domains of the executive functions: the inhibition abilities and the capacity to co-ordinate simultaneously storage and processing of information. Moreover, the performance on these factors is correlated to different anterior and posterior cortical areas.

[Working memory: a neuropsychologic and cerebral imagery approach]. / La mémoire de travail: une approche neuropsychologique et par imagerie cérébrale.

The working memory model proposed by Baddeley and Hitch has frequently been used in cognitive psychology and neuropsychological studies. This model consists of several interacting components, responsible for the storage and processing of the information stored in working memory. Many neuropsychological and functional imagery data are consistent with that formulation of working memory. Moreover, many cognitive tasks have been specifically designed to explore particular aspects of working memory functioning. Taken as a whole, these data confirm that the working memory model remains a useful theoretical framework to explore memory functioning both in normal subjects and in pathological conditions.