Integrity of white matter microstructure in alcoholics with and without Korsakoff's syndrome Human Brain Mapping Integrity of white matter microstructure in alcoholics with and without Korsakoff's syndrome

International audienceAlcohol dependence results in two different clinical forms: "uncomplicated" alcoholism (UA) and Korsakoff's syndrome (KS). Certain brain networks are especially affected in UA and KS: the frontocerebellar circuit (FCC) and the Papez circuit (PC). Our aims were (1) to describe the profile of white matter (WM) microstructure in FCC and PC in the two clinical forms, (2) to identify those UA patients at risk of developing KS using their WM microstructural integrity as a biomarker. Tract-based spatial statistics and nonparametric voxel-based permutation tests were used to compare diffusion tensor imaging (DTI) data in 7 KS, 20 UA, and 14 healthy controls. The two patient groups were also pooled together and compared to controls. k-means classifications were then performed on mean fractional anisotropy values of significant clusters across all subjects for two fiber tracts from the FCC (the middle cerebellar peduncle and superior cerebellar peduncle) and two tracts from the PC (fornix and cingulum). We found graded effects of WM microstructural abnormalities in the PC of UA and KS. UA patients classified at risk of developing KS using fiber tracts of the PC from DTI data also had the lowest scores of episodic memory. That finding suggests that WM microstructure could be used as a biomarker for early detection of UA patients at risk of developing KS

Looking beyond the hippocampus: old and new neurological targets for understanding memory disorders

Although anterograde amnesia can occur after damage in various brain sites, hippocampal dysfunction is usually seen as the ultimate cause of the failure to learn new episodic information. This assumption is supported by anatomical evidence showing direct hippocampal connections with all other sites implicated in causing anterograde amnesia. Likewise, behavioural and clinical evidence would seem to strengthen the established notion of an episodic memory system emanating from the hippocampus. There is, however, growing evidence that key, interconnected sites may also regulate the hippocampus, reflecting a more balanced, integrated network that enables learning. Recent behavioural evidence strongly suggests that medial diencephalic structures have some mnemonic functions independent of the hippocampus, which can then act upon the hippocampus. Anatomical findings now reveal that nucleus reuniens and the retrosplenial cortex provide parallel, disynaptic routes for prefrontal control of hippocampal activity. There is also growing clinical evidence that retrosplenial cortex dysfunctions contribute to both anterograde amnesia and the earliest stages of Alzheimer's disease, revealing the potential significance of this area for clinical studies. This array of findings underlines the importance of redressing the balance and the value of looking beyond the hippocampus when seeking to explain failures in learning new episodic information