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Richard Levy

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5 papers
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5

YNICL Journal 2022 Journal Article

An ecological approach to identify distinct neural correlates of disinhibition in frontotemporal dementia

  • Delphine Tanguy
  • Bénédicte Batrancourt
  • Alfonso Estudillo-Romero
  • John S.H. Baxter
  • Isabelle Le Ber
  • Arabella Bouzigues
  • Valérie Godefroy
  • Aurélie Funkiewiez

Disinhibition is a core symptom of many neurodegenerative diseases, particularly frontotemporal dementia, and is a major cause of stress for caregivers. While a distinction between behavioural and cognitive disinhibition is common, an operational definition of behavioural disinhibition is still missing. Furthermore, conventional assessment of behavioural disinhibition, based on questionnaires completed by the caregivers, often lacks ecological validity. Therefore, their neuroanatomical correlates are non-univocal. In the present work, we used an original behavioural approach in a semi-ecological situation to assess two specific dimensions of behavioural disinhibition: compulsivity and social disinhibition. First, we investigated disinhibition profile in patients compared to controls. Then, to validate our approach, compulsivity and social disinhibition scores were correlated with classic cognitive tests measuring disinhibition (Hayling Test) and social cognition (mini-Social cognition & Emotional Assessment). Finally, we disentangled the anatomical networks underlying these two subtypes of behavioural disinhibition, taking in account the grey (voxel-based morphometry) and white matter (diffusion tensor imaging tractography). We included 17 behavioural variant frontotemporal dementia patients and 18 healthy controls. We identified patients as more compulsive and socially disinhibited than controls. We found that behavioural metrics in the semi-ecological task were related to cognitive performance: compulsivity correlated with the Hayling test and both compulsivity and social disinhibition were associated with the emotion recognition test. Based on voxel-based morphometry and tractography, compulsivity correlated with atrophy in the bilateral orbitofrontal cortex, the right temporal region and subcortical structures, as well as with alterations of the bilateral cingulum and uncinate fasciculus, the right inferior longitudinal fasciculus and the right arcuate fasciculus. Thus, the network of regions related to compulsivity matched the "semantic appraisal" network. Social disinhibition was associated with bilateral frontal atrophy and impairments in the forceps minor, the bilateral cingulum and the left uncinate fasciculus, regions corresponding to the frontal component of the "salience" network. Summarizing, this study validates our semi-ecological approach, through the identification of two subtypes of behavioural disinhibition, and highlights different neural networks underlying compulsivity and social disinhibition. Taken together, these findings are promising for clinical practice by providing a better characterisation of inhibition disorders, promoting their detection and consequently a more adapted management of patients.

YNIMG Journal 2007 Journal Article

A novel approach to clinical–radiological correlations: Anatomo-Clinical Overlapping Maps (AnaCOM): Method and validation

  • Serge Kinkingnéhun
  • Emmanuelle Volle
  • Mélanie Pélégrini-Issac
  • Jean-Louis Golmard
  • Stéphane Lehéricy
  • Foucaud du Boisguéheneuc
  • Sandy Zhang-Nunes
  • Danielle Sosson

We present a new clinical–radiological correlation method (AnaCOM) that aims at establishing structure–function relationships. We validated AnaCOM by assessing the location of lesions that are associated with altered performances in a well-studied task: the verbal fluency task. We retrospectively reviewed 64 brain-damaged patients who had focal lesions in a variety of cortical sites due to stroke, hemorrhage or tumor surgery. All patients were tested for verbal fluency at the time of the MRI examination. MRI volumes were normalized using a mask covering brain lesions and artifacts. The brain lesions were then segmented using the normalized MRI. In each patient, a verbal fluency score was assigned to each voxel in the segmented area. Subsequently, segmentations were superimposed and voxels were gathered in clusters defined by the overlap of the patients' lesion. For each cluster, the scores were statistically compared to those obtained by controls for the same task. This process allowed the construction of cluster-by-cluster statistical maps of anatomo-clinical correlations. As expected, the statistical map indicated that two regions were significantly associated with a deficit in the fluency task: one located in Broca's area and the other in the preSMA. AnaCOM does not require a priori selection of the location of lesions or task scores. The method complements the functional imaging techniques, as it tells which regions are necessary for a given function and it explores cortical regions as well as the white matter.

YNIMG Journal 2005 Journal Article

Cognitive control and brain resources in major depression: An fMRI study using the n-back task

  • Philippe-Olivier Harvey
  • Philippe Fossati
  • jean-baptiste pochon
  • Richard Levy
  • Guillaume LeBastard
  • Stéphane Lehéricy
  • Jean-François Allilaire
  • Bruno Dubois

Several neuroimaging studies have reported ‘hypofrontality’ in depressed patients performing a cognitive challenge compared to control subjects. Hypofrontality in depression is likely associated with an impaired behavioral performance. It is unclear whether this impaired performance is the consequence or the cause of hypofrontality. Consequently, we proposed to compare the cerebral activity of depressed patients and healthy subjects while controlling for the level of performance. Ten individuals meeting DSM-IV criteria for Major Depression and 10 healthy controls were tested with a verbal version of the n-back task during fMRI scanning. The working memory load was manipulated across the experiment (1, 2, 3-back) to increase the cognitive demands. fMRI data were acquired on a 1. 5-T GE scanner and analyzed using SPM99 software. We did not find any difference between groups in both performance and reaction times for each level of complexity of the n-back task. Depressed patients and control subjects showed bilateral activation of the lateral prefrontal cortex, anterior cingulate and parietal cortex. Activation of these regions was modulated by the complexity of the task. Within this n-back neural network, depressed patients showed greater activation of the lateral prefrontal cortex and the anterior cingulate compared to healthy subjects. This study provides evidence that depressed patients need greater activation within the same neural network to maintain a similar level of performance as controls during a working memory task. Our findings suggest that depression may impair the cognitive capacity of depressed patients by recruiting more brain resources than controls during cognitive control.

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