FDG-PET Findings in the Wernicke-Korsakoff Syndrome

Selective septohippocampal – but not forebrain amygdalar – cholinergic dysfunction in diencephalic amnesia

“…There are two disease features of thiamine deficiency-induced amnesia that could result in this selective hippocampal dysfunction: (1) As the present study suggests, the loss of ChAT positive neurons in the MS/DB produces an inadequate activation of the hippocampus during behavioral testing; (2) Lesions of discrete diencephalic regions (anterior thalamus, mammillary bodies) can lead to memory impairment as well as changes in hippocampal physiological activity [20,45,54,55,58]. Additional research is needed comparing the two factors before we can identify the primary mechanisms for ACh dysfunction in diencephalic amnesia.…”

“…Damage to certain nuclei and fiber systems within the diencephalon interrupts the flow of information between key memory structures and thus causes severe and long-lasting amnesia [25,29,45]. Although there is evidence that lesions to particular diencephalic nuclei result in memory impairment in their own right, there is also evidence that damage to diencephalic nuclei can disrupt memory circuits leading to dysfunction in other regions of the brain [4,29,45,49,53].Corresponding author: Lisa M. Savage, Department of Psychology, Binghamton University, State University of New York, Binghamton, NY, 13902, e-mail: lsavage@binghamton.edu, fax: 607-777-4890. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.…”

“…These changes, along with the white matter loss that occurs in key fiber tracts from the diencephalon after PTD treatment [27], suggest that thiamine deficiency likely causes system level dysfunction. There is neurobiological evidence that even discrete diencephalic damage alters the activation of other limbic regions -in particular the hippocampus [see 20,45,49]. Thus, damage to the diencephalon produced by thiamine deficiency could produce dysfunction in other limbic regions.…”

Blunted hippocampal, but not striatal, acetylcholine efflux parallels learning impairment in diencephalic-lesioned rats

“…Despite the lack of lesions or cell loss to the hippocampus in WKS (Reed et al, 2003) or PTD (Langlais, Zhang, & Savage, 1996), there is evidence of global limbic system dysfunction in this disorder and the animal model. Degeneration is reported in key limbic system fiber tracts such as the mammilothalamic tract and fornix in WKS and PTD (Langlais & Zhang, 1997;Sullivan & Marsh, 2003).…”

“…From a clinical standpoint, it is debated whether there is a functional distinction between diencephalic and temporal lobe amnesia (Aggleton & Brown, 1999;Caulo et al, 2005). This is supported by human imaging studies as well as electrophysiological, gene expression, and neurochemical data from animal models that suggest that diencephalic damage has a profound effect on hippocampal functioning (Jenkins, Dias, Amin, Brown, & Aggleton, 2002;Reed et al, 2003;Savage, Chang, & Gold, 2003;Vertes, Hoover, & Viana Di Prisco, 2004).…”