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See detailVoxel-based analysis of posterior cingulated cortex metabolism in Alzheimer’s disease : effect of dementia severity and age.
WITHOFS, Nadia ULg; SALMON, Eric ULg; LAUREYS, Steven ULg et al

in PROCEEDINGS OF XIIIth SYMPOSIUM OF THE BELGIAN SOCIETY OF NUCLEAR MEDICINE (2007, May)

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See detailSocial mind representation: Where does it fail in frontotemporal dementia?
Ruby, P.; Schmidt, Christina ULg; Hogge, Michaël et al

in Journal of Cognitive Neuroscience (2007), 19(4), 671-683

We aimed at investigating social disability and its cerebral correlates in frontotemporal dementia (FTD). To do so, we contrasted answers of patients with early-stage FTD and of their relatives on ... [more ▼]

We aimed at investigating social disability and its cerebral correlates in frontotemporal dementia (FTD). To do so, we contrasted answers of patients with early-stage FTD and of their relatives on personality trait judgment and on behavior prediction in social and emotional situations. Such contrasts were compared to control contrasts calculated with answers of matched controls tested with their relatives. in addition, brain metabolism was measured in patients with positron emission tomography and the [F-18]fluorodeoxyglucose method. Patients turned out to be as accurate as controls in describing their relative's personality, but they failed to predict their relative's behavior in social and emotional circumstances. Concerning the self, patients were impaired both in Current personality assessment and in prediction of their own behavior. Those two self-evaluation measures did not correlate. Only patients' anosognosia for social behavioral disability was found to be related to decreased metabolic activity in the left temporal pole. Such results suggest that anosognosia for social disability in FTD originates in impaired processing of emotional autobiographical information, leading to a self-representation that does not match current behavior. Moreover, we propose that perspective-taking disability participates in anosognosia, preventing patients from correcting their inaccurate self-representation based on their relative's perspective. [less ▲]

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See detailShort-term memory and the left intraparietal sulcus: Focus of attention? Further evidence from a face short-term memory paradigm
Majerus, Steve ULg; Bastin, Christine ULg; Poncelet, Martine ULg et al

in NeuroImage (2007), 35(1), 353-367

This study explored the validity of an attentional account for the involvement of the left intraparietal sulcus (IPS) in visual STM tasks. This account considers that during STM tasks, the IPS acts as an ... [more ▼]

This study explored the validity of an attentional account for the involvement of the left intraparietal sulcus (IPS) in visual STM tasks. This account considers that during STM tasks, the IPS acts as an attentional modulator, maintaining activation in long-term memory networks that underlie the initial perception and processing of the specific information to be retained. In a recognition STM paradigm, we presented sequences of unfamiliar faces and instructed the participants to remember different types of information: either the identity of the faces or their order of presentation. We hypothesized that, if the left IPS acts as an attentional modulator, it should be active in both conditions, but connected to different neural networks specialized in serial order or face identity processing. Our results showed that the left IPS was activated during both order and identity encoding conditions, but for different reasons. During order encoding, the left IPS showed functional connectivity with order processing areas in the right IPS, bilateral premotor and cerebellar cortices, reproducing earlier results obtained in a verbal STM experiment. During identity encoding, the left IPS showed preferential functional connectivity with right temporal, inferior parietal and medial frontal areas involved in detailed face processing. These results not only support an attentional account of left IPS involvement in visual STM, but given their similarity with previous results obtained for a verbal STM task, they further highlight the importance of the left IPS as an attentional modulator in a variety of STM tasks. [less ▲]

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See detailMapping the updating process: common and specific brain activations across different versions of the running span task
Collette, Fabienne ULg; Van der Linden, Martial ULg; Laureys, Steven ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2007), 43(1), 146-158

Neuroimaging studies exploring the neural substrates of executive functioning have only rarely investigated whether the non-executive characteristics of the experimental executive tasks could contribute ... [more ▼]

Neuroimaging studies exploring the neural substrates of executive functioning have only rarely investigated whether the non-executive characteristics of the experimental executive tasks could contribute to the observed brain activations. The aim of this study was to determine cerebral activity in three different tasks involving the updating executive function. The experimental updating tasks required subjects to process strings of items (respectively letters, words, and sounds) of unknown lengths, and then to recall or identify a specific number of presented items. Conjunction and functional connectivity analyses demonstrated that the cerebral areas activated by all three experimental tasks are the left frontopolar cortex, bilateral dorsolateral prefrontal and premotor cortex, bilateral intraparietal sulcus, right inferior parietal lobule and cerebellum. Some regions of this network appear to be more specific to each updating task. These results clearly indicate that the neural substrates underlying a specific executive process (in this case, updating) are modulated by the exact requirements of the task (such as the material to process or the kind of response) and the specific cognitive processes associated with updating. [less ▲]

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See detailVoxel-based analysis of dementia severity versus age on cerebral metabolic dysfunction in Alzheimer’s disease.
WITHOFS, Nadia ULg; SALMON, Eric ULg; LAUREYS, Steven ULg et al

in Journal of Nuclear Medicine (The) (2007), 48(SUPPL), 172

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See detailA multicomponent exploration of verbal short-term storage deficits in normal aging and Alzheimer’s disease
Peters, Frédéric; Majerus, Steve ULg; Olivier, Laurence et al

in Journal of Clinical & Experimental Neuropsychology (2007), 29(4), 405-417

Although many studies have shown diminished performance in verbal short-term memory tasks in normal aging and Alzheimer's disease (AD), the cognitive processes responsible for this verbal short-term ... [more ▼]

Although many studies have shown diminished performance in verbal short-term memory tasks in normal aging and Alzheimer's disease (AD), the cognitive processes responsible for this verbal short-term storage (STS) impairment are still unclear for both populations. We explored verbal STS functioning in patients with AD, elderly participants, and young participants, by investigating a series of processes that could underlie STS impairments in normal elderly and AD populations. The processes we investigated were (a) the influence of lexical and sublexical language knowledge on short-term storage performance, (b) functioning of the phonological loop component via word length and phonological similarity effects, and (c) executive control processes (coordination and integration). For the AD and elderly groups, the influence of language knowledge on verbal STS performance and the functioning of the phonological loop were preserved. In contrast, the AD group showed deficits for coordination and integration processes. Our results suggest that the verbal STS deficit observed in AD patients is related to impaired executive control processes. On the other hand, language-related processes underlying passive storage capacity seem to be preserved. [less ▲]

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See detailTherapeutic armamentarium in neurology: the birth of a new era
Belachew, Shibeshih ULg; Magis, Delphine ULg; Lievens, Isabelle ULg et al

in Revue Médicale de Liège (2007), 62(5-6), 432-448

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into ... [more ▼]

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into history, and the field is now vibrant with new treatments and hope even for patients with the worst neurodegenerative diseases. We summarized in the present review the latest major advances in therapeutic principles and practice for some of the most frequent chronic neurological disorders such as headaches, epilepsy, multiple sclerosis, dementias, Parkinson's disease, sleep/wake disturbances and peripheral neuropathies. We cannot cure or prevent, but we can now halt or control symptoms and disease progression to provide physical and psychological relief, and a better quality of life for patients who suffer from these otherwise devastating neurological conditions. [less ▲]

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See detailA Synthesis of Functional Neuroimaging in the Frontal Variant of Frontotemporal Dementia
Salmon, Eric ULg; Garraux, Gaëtan ULg; Collette, Fabienne ULg

in Current Medical Imaging Reviews (2007), 3(2), 117-121

The frontal variant of frontotemporal dementia (fvFTD) is clinically characterized by a disruption of the social behaviour. Frontotemporal decrease of activity on functional imaging is an independent ... [more ▼]

The frontal variant of frontotemporal dementia (fvFTD) is clinically characterized by a disruption of the social behaviour. Frontotemporal decrease of activity on functional imaging is an independent marker of the disease. Principal component analysis of cerebral functional images reveals one ensemble comprising both frontal lobes, and two lateralized clusters comprising temporal and subcallosal frontal regions. Executive dysfunction and verbal difficulties are shown to interact in fvFTD, and they are related to large scale frontal and temporal neural networks in the disease. The neural substrate of the memory impairments in patients with fvFTD is also heterogeneous, since correlations were observed with frontal activity, but also with medial temporal atrophy. Behavioural changes are the hallmarks of fvFTD. Apathy is consistently related to frontal involvement, while disinhibition occurs in patients with predominant posterior orbitofrontal and temporal involvement. The consequences of lateralized brain lesions remain a matter of debate, since impulsive and compulsive behaviour was evenly related to right or left temporal involvement in fvFTD. Those patients know social rules, but they are impaired in assessing the importance of social transgressions and in recognizing emotions. Processing transgressions of social norms results in a complex activation of medial prefrontal, orbitofrontal and temporal regions in control populations. The variable decrease in these regional activities observed in different fvFTD patients would explain their complex, individual social disturbance. [less ▲]

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See detailNeuropsychiatric syndromes in dementia - Results from the European Alzheimer Disease Consortium: Part I
Aalten, Pauline; Verhey, Frans R. J.; Boziki, Marina et al

in Dementia & Geriatric Cognitive Disorders (2007), 24(6), 457-463

Background/Aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD). Methods: Cross ... [more ▼]

Background/Aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD). Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD. Copyright (c) 2007 S. Karger AG, Basel. [less ▲]

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See detailNeural correlates of anosognosia for cognitive impairment in Alzheimer's disease
Salmon, Eric ULg; Perani, D.; Herholz, K. et al

in Human Brain Mapping (2006), 27(7), 588-597

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients ... [more ▼]

We explored the neural substrate of anosognosia for cognitive impairment in Alzheimer's disease (AD). Two hundred nine patients with mild to moderate dementia and their caregivers assessed patients' cognitive impairment by answering a structured questionnaire. Subjects rated 13 cognitive domains as not impaired or associated with mild, moderate, severe, or very severe difficulties, and a sum score was calculated. Two measures of anosognosia were derived. A patient's self assessment, unconfounded by objective measurements of cognitive deficits such as dementia severity and episodic memory impairment, provided an estimate of impaired self-evaluative judgment about cognition in AD. Impaired self-evaluation was related to a decrease in brain metabolism measured with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in orbital prefrontal cortex and in medial temporal structures. In a cognitive model of anosognosia, medial temporal dysfunction might impair a comparison mechanism between current information on cognition and personal knowledge. Hypoactivity in orbitofrontal cortex may not allow AD patients to update the qualitative judgment associated with their impaired cognitive abilities. Caregivers perceived greater cognitive impairments than patients did. The discrepancy score between caregiver's and patient's evaluations, an other measure of anosognosia, was negatively related to metabolic activity located in the temporoparietal junction, consistent with an impairment of self-referential processes and perspective taking in AD. [less ▲]

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See detailExploration of the neural substrates of executive functioning by functional neuroimaging
Collette, Fabienne ULg; Hogge, Michaël; Salmon, Eric ULg et al

in Neuroscience (2006), 139(1), 209-221

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 ... [more ▼]

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. [less ▲]

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See detailDecomposition of metabolic brain clusters in the frontal variant of frontotemporal dementia
Salmon, Eric ULg; Kerrouche, Nacer; Herholz, Karl et al

in NeuroImage (2006), 30(3), 871-878

Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research ... [more ▼]

Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research program the principal brain clusters characterized by a common variability in cerebral metabolism in FTD. Seventy patients with frontal variant (fv) FTD were selected according to international clinical recommendations; principal component analysis (PCA) was performed on FDG-PET metabolic images, looking for covariance clusters in this large population. A first metabolic cluster included most of the lateral and medial prefrontal cortex, bilaterally; PC1 scores correlated with performances on memory and executive neuropsychological tasks. Moreover, FDG-PET images in fv-FTD were further characterized by a metabolic covariance in two clusters comprising the subcallosal medial frontal region, the temporal pole, medial temporal structures and the striatum, separately in the left and in the right hemisphere. The study provides original data-driven arguments for metabolic involvement of separate brain clusters in the rostral limbic system, corresponding to pathological poles differentially affected in each FTD patient. [less ▲]

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See detailOrbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine
Fumal, Arnaud ULg; Laureys, Steven ULg; Di Clemente, Laura et al

in Brain (2006), 129(Pt 2), 543-550

The way in which medication overuse transforms episodic migraine into chronic daily headache is unknown. To search for candidate brain areas involved in this process, we measured glucose metabolism with ... [more ▼]

The way in which medication overuse transforms episodic migraine into chronic daily headache is unknown. To search for candidate brain areas involved in this process, we measured glucose metabolism with 18-FDG PET in 16 chronic migraineurs with analgesic overuse before and 3 weeks after medication withdrawal and compared the data with those of a control population (n = 68). Before withdrawal, the bilateral thalamus, orbitofrontal cortex (OFC), anterior cingulate gyrus, insula/ventral striatum and right inferior parietal lobule were hypometabolic, while the cerebellar vermis was hypermetabolic. All dysmetabolic areas recovered to almost normal glucose uptake after withdrawal of analgesics, except the OFC where a further metabolic decrease was found. A subanalysis showed that most of the orbitofrontal hypometabolism was due to eight patients overusing combination analgesics and/or an ergotamine-caffeine preparation. Medication overuse headache is thus associated with reversible metabolic changes in pain processing structures like other chronic pain disorders, but also with persistent orbitofrontal hypofunction. The latter is known to occur in drug dependence and could predispose subgroups of migraineurs to recurrent analgesic overuse. [less ▲]

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See detailVariability in the impairments of recognition memory in patients with frontal lobe lesions
Bastin, Christine ULg; Van der Linden, Martial ULg; Lekeu, Françoise ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2006), 42(7), 971-1058

Fourteen patients with frontal lobe lesions and 14 normal subjects were tested on a recognition memory task that required discriminating between target words, new words that are synonyms of the targets ... [more ▼]

Fourteen patients with frontal lobe lesions and 14 normal subjects were tested on a recognition memory task that required discriminating between target words, new words that are synonyms of the targets and unrelated distractors. A deficit was found in 12 of the patients. Moreover, three different patterns of recognition impairment were identified: (I) poor memory for targets, (II) normal hits but increased false recognitions for both types of distractors, (III) normal hit rates, but increased false recognitions for synonyms only. Differences in terms of location of the damage and behavioural characteristics between these subgroups were examined. An encoding deficit was proposed to explain the performance of patients in subgroup I. The behavioral patterns of the patients in subgroups II and III could be interpreted as deficient postretrieval verification processes and an inability to recollect item-specific information, respectively. [less ▲]

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See detailThe left intraparietal sulcus and verbal short-term memory: Focus of attention or serial order ?
Majerus, Steve ULg; Poncelet, Martine ULg; Van der Linden, Martial ULg et al

in Neuroimage (2006), 32(2), 880-891

One of the most consistently activated regions during verbal short-term memory (STM) tasks is the left intraparietal sulcus (IPS). However, its precise role remains a matter of debate. While some authors ... [more ▼]

One of the most consistently activated regions during verbal short-term memory (STM) tasks is the left intraparietal sulcus (IPS). However, its precise role remains a matter of debate. While some authors consider the IPS to be a specific store for serial order information, other data suggest that it serves a more general function of attentional focalization. In the current fMRI experiment, we investigated these two hypotheses by presenting different verbal STM conditions that probed recognition for word identity or word order and by assessing functional connectivity of the left IPS with distant brain areas. If the IPS has a role of attentional focalization, then it should be involved in both order and item conditions, but it should be connected to different brain regions, depending on the neural substrates involved in processing the different types of information (order versus phonological/orthographic) to be remembered in the item and order STM conditions. We observed that the left IPS was activated in both order and item STM conditions but for different reasons: during order STM, the left IPS was functionally connected to serial/temporal order processing areas in the right IPS, premotor and cerebellar cortices, while during item STM, the left IPS was connected to phonological and orthographic processing areas in the superior temporal and fusiform gyri. Our data support a position considering that the left IPS acts as an attentional modulator of distant neural networks which themselves are specialized in processing order or language representations. More generally, they strengthen attention-based accounts of verbal STM. [less ▲]

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See detailOrbitofrontal dysfunction related to both apathy and disinhibition in frontotemporal dementia
Peters, Frederic; Perani, Daniela; Herholz, Karl et al

in Dementia & Geriatric Cognitive Disorders (2006), 21(5-6), 373-379

Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral ... [more ▼]

Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex ( 6, 28, - 24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects ( 4, 22, - 22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD. Copyright (C) 2006 S. Karger AG, Basel. [less ▲]

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See detailPrincipes d'adaptation cognitive dans les démences
Salmon, Eric ULg; Adam, Stéphane ULg; Lekeu, Françoise ULg et al

Book published by Kluver (2006)

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See detailEXploration des processus inhibiteurs dans le vieillissement normal et la maladie d'Alzheimer
Collette, Fabienne ULg; Adam, Stéphane ULg; Hogge, Michaël et al

Conference (2005, November)

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See detailHeterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease
Anchisi, D.; Borroni, B.; Franceschi, M. et al

in Archives of Neurology (2005), 62(11), 1728-1733

Background: Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic ... [more ▼]

Background: Subjects with amnesic mild cognitive impairment (aMCI) may include patients at high risk for progression to Alzheimer disease (AD) and a population with different underlying pathologic conditions. Objective: To evaluate the potential roles of positron emission tomography with fluodeoxyglucose F 18 ((18)FDG-PET) and memory scores in identifying subjects with aMCI and in predicting progression to dementia. Design, Setting, and Patients: Sixty-seven patients at European centers for neurologic and AD care who were diagnosed as having aMCI each underwent an extensive clinical and neuropsychological examination and an (18)FDG-PET study. Forty-eight subjects were followed up periodically for at least I year, and progression to dementia was evaluated. Main Outcome Measures: Brain glucose metabolism and memory scores. Results: Fourteen subjects with aMCI who converted to AD within 1 year showed bilateral hypometabolism in the inferior parietal, posterior cingulate, and medial temporal cortex. Subjects with "stable" aMCI presented with hypometabolism in the dorsolateral frontal cortex. The severity of memory impairment, as evaluated by the California Verbal Learning Test-Long Delay Free Recall scores, correlated with the following brain metabolic patterns: scores less than 7 were associated with a typical (18)FDG-PET AD pattern, and scores of 7 or higher were associated with hypornetabolism in the dorsolateral frontal cortex and no progression to AD. Conclusion: These data provide evidence for clinical and functional heterogeneity among subjects with aMCI and suggest that (18)FDG-PET findings combined with memory scores may be useful in predicting short-term conversion to AD. [less ▲]

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