title: Why do patients with neurodegenerative frontal syndrome fail to answer: 'In what way are an orange and a banana alike?'.
abstract: Concept formation is the ability to create an abstract link between dissimilar objects or thoughts and is crucial for abstract and creative thinking. This process is related to the integrity of the prefrontal cortex, given the altered performances reported in patients with frontal damage, particularly those suffering from the behavioural variant of frontotemporal dementia. However, the cognitive mechanisms and neural bases of verbal concept formation are not clearly understood. The present study was aimed at addressing the following unresolved issues regarding concept formation in the field of neurology and cognitive neuroscience: (i) Are alterations in concept formation specific to frontotemporal dementia or are they also present in other cortical neurodegenerative disorders such as Alzheimer's disease? (ii) Is impaired performance in concept formation due to cortical lesions specific to frontotemporal dementia or to a cortico-subcortical frontal syndrome? and (iii) What are the cognitive mechanisms and neural bases underlying concept formation? To address these questions, we designed the Verbal Concept Formation Task, an experimental paradigm based on the similarities test. Patients presenting with severe frontal dysfunction (frontotemporal dementia, n = 18, and the Richardson form of progressive supranuclear palsy, n = 21) or with medial temporal pathology (amnestic mild cognitive impairment or Alzheimer's disease, n = 14) and healthy participants (n = 18) were given the Verbal Concept Formation Task and a large battery of neuropsychological tests. In addition, all participants underwent 3D T1-weighted MRI to analyse grey matter volume using voxel-based morphometry. Frontal patients were significantly impaired on the Verbal Concept Formation Task as compared to non-frontal participants (P = 0.00001). Global performance score was positively correlated with scores in cognitive tasks assessing executive functions and with grey matter volume in several areas, mostly in the frontal-basal-ganglion network. Two types of errors were observed in frontal patients. The most frequent was discriminating instead of grouping items ('linking deficit'). Patients also linked items on a concrete instead of an abstract basis ('abstraction deficit'). Linking and abstraction deficits were related to partially different areas: the linking deficit to the dorsal anterior cingulate cortex, right middle frontal gyrus and both inferior parietal lobules and the abstraction deficit to the head of the caudate nuclei and the left superior frontal gyrus. These data suggest that verbal concept formation requires the integrity of the prefrontal-basal-ganglion functional network. In addition, it can be divided into two distinct cognitive processes, which are underlain by two partially different neural networks.
authors.affiliation: 1 Neurology of Memory and Language Unit, Department of Neurology, Centre Hospitalier Sainte-Anne, 75014, Paris, France 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lagarde
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 3 Centre de NeuroImagerie de Recherche (CENIR), Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France 4 Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Valabrègue
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 4 Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France 6 AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Neurology, 75013, Paris, France 7 INSERM, Centre d'Investigation Clinique, CIC-1422, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Corvol
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Garcin
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Volle
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 4 Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France 6 AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Neurology, 75013, Paris, France 8 National Reference Centre on Rare Dementias, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Ber
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 4 Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France 6 AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Neurology, 75013, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vidailhet
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 4 Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France 6 AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Neurology, 75013, Paris, France 8 National Reference Centre on Rare Dementias, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, 75013, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.affiliation: 2 INSERM, UMR_S1127, ICM, F-75013, Paris, France 4 Sorbonne Universités, UPMC Univ Paris 06, UMR_S1127, ICM, F-75013, Paris, France 5 CNRS, UMR_7225, ICM, F-75005, 75013, Paris, France 9 AP-HP, Hôpital Saint-Antoine, Department of Neurology, 75012, Paris, France richard.levy@sat.aphp.fr.
authors.forename: Richard
authors.initials: R
authors.lastname: Levy
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000473:pathology / Q000523:psychology; D001927:Brain Diseases / Q000523:psychology*; D003210:Concept Formation; D005260:Female; D005625:Frontal Lobe; D057180:Frontotemporal Dementia / Q000473:pathology / Q000523:psychology*; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000523:psychology*; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011597:Psychomotor Performance
keywords: basal ganglia; executive functions; frontal lobe; frontotemporal dementia; neuropsychiatry: imaging