1. Dissociating thalamic alterations in Alcohol Use Disorder defines specificity of Korsakoff syndrome
- Author
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Ludivine Ritz, François Vabret, Hélène Beaunieux, Shailendra Segobin, Laurent Urso, Anne-Lise Pitel, Céline Boudehent, Coralie Lannuzel, Francis Eustache, Nicolas Cabé, Alice Laniepce, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Addictologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d’Addictologie [CH Roubaix], CH de Roubaix, This study was funded by Fondation pour la Recherche Medicale (FRM, ING20140129160), ANR Retour post-doctorant 2010, Conseil Regional Basse Normandie, and MILDECA., U1077, U1077, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Neuropsychologie et imagerie de la mémoire humaine ( NIMH ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -École pratique des hautes études ( EPHE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Service d’Addictologie [CHU Caen]
- Subjects
0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Thalamus ,mediodorsal thalamic nuclei ,Hippocampus ,Amnesia ,behavioral disciplines and activities ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,medicine ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Prefrontal cortex ,Wernicke–Korsakoff syndrome ,[ SDV ] Life Sciences [q-bio] ,business.industry ,Papez circuit ,segmentation ,Precentral gyrus ,Korsakoff’s syndrome ,medicine.disease ,diffusion tensor imaging ,anterior thalamic nuclei ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Neurology (clinical) ,medicine.symptom ,Korsakoff's syndrome ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
International audience; The thalamus, a relay organ consisting of several nuclei, is shared between the frontocerebellar circuit and the Papez circuit, both particularly affected in alcohol use disorder. Shrinkage of the thalamus is known to be more severe in alcoholics with Korsakoff's syndrome than in those without neurological complications (uncomplicated alcoholics). While thalamic atrophy could thus be a key factor explaining amnesia in Korsakoff's syndrome, the loci and nature of alterations within the thalamic nuclei in uncomplicated alcoholics and alcoholics with Korsakoff's syndrome remains unclear. Indeed, the literature from animal and human models is disparate regarding whether the anterior thalamic nuclei, or the mediodorsal nuclei are particularly affected and would be responsible for amnesia. Sixty-two participants (20 healthy controls, 26 uncomplicated alcoholics and 16 patients with Korsakoff's syndrome) underwent a diffusion tensor imaging sequence and T1-weighted MRI. State-of-the-art probabilistic tractography was used to segment the thalamus according to its connections to the prefrontal cortex and cerebellar Cruses I and II for the frontocerebellar circuit's executive loop, the precentral gyrus and cerebellar lobes IV-VI for the frontocerebellar circuit's motor loop, and hippocampus for the Papez circuit. The connectivity and volumes of these parcellations were calculated. Tractography showed that the hippocampus was principally connected to the anterior thalamic nuclei while the prefrontal cortex was principally connected to the mediodorsal nuclei. The fibre pathways connecting these brain regions and their respective thalamic nuclei have also been validated. ANCOVA, with age and gender as covariates, on connectivity measures showed abnormalities in both patient groups for thalamic parcellations connected to the hippocampus only [F(2,57) = 12.1; P < 0.0001; η2 = 0.2964; with graded effects of the number of connections from controls to uncomplicated alcoholics to Korsakoff's syndrome]. Atrophy, on the other hand, was observed for the prefrontal parcellation in both patient groups and to the same extent compared to controls [F(2,56) = 18.7; P < 0.0001; η2 = 0.40]. For the hippocampus parcellation, atrophy was found in the Korsakoff's syndrome group only [F(2,56) = 5.5; P = 0.006; η2 = 0.170, corrected for multiple comparisons using Bonferroni, P < 0.01]. Post hoc Tukey's test for unequal sample sizes, healthy controls > patients with Korsakoff's syndrome (P = 0.0036). Two different mechanisms seem to affect the thalamus. In the frontocerebellar circuit, atrophy of the mediodorsal nuclei may lead to the alterations, whereas in the Papez circuit, disconnection between the anterior nuclei and hippocampus may be the leading factor. Shrinkage of the anterior nuclei could be specific to patients with Korsakoff's syndrome, hence a potential neuroimaging marker of its pathophysiology, or more generally of thalamic amnesia for which Korsakoff's syndrome has historically been used as a model.
- Published
- 2019