Cognitive Impairment in Temporal Lobe Epilepsy: Alterations in the Basal Forebrain Cholinergic System

Temporal Lobe Epilepsy (TLE) often leads to cognitive decline. The Basal Forebrain Cholinergic System (BFCS), essential for memory processes, may play a critical role. This study investigates BFCS alterations, associated white matter tracts, and cognitive correlations in TLE patients.

We analyzed 100 unilateral TLE patients and 25 healthy controls. Neuropsychological assessments included the Wechsler Memory Scale-Revised and the Rey Complex Figure Test. Regions of interest (ROIs), such as the hippocampus, amygdala, and dorsolateral prefrontal cortex, were identified using the AAL3 atlas and SPM 8 Anatomy toolbox. BFCS tract integrity was assessed using FSL probabilistic tractography, focusing on FA and MD values.

Both left TLE (LTLE) and right TLE (RTLE) groups displayed significant deficits in memory quotient, verbal/nonverbal memory, and visuospatial working memory, with hippocampal sclerosis (HS) patients showing greater impairment. LTLE patients exhibited extensive BFCS impairment versus controls, with reduced FA (bilateral hippocampus/amygdala, all p < 0.01) and elevated MD (bilateral hippocampus p < 0.05; bilateral amygdala p < 0.01; DLPFC p < 0.05). RTLE showed localized damage: decreased FA (left hippocampus/right amygdala, both p < 0.05) and increased DLPFC MD (p < 0.05). HS intensified BFCS-right hippocampal and bilateral amygdala damage in TLE. Correlation analyses indicated positive associations between BFCS-right hippocampal FA and verbal and nonverbal memory, whereas its MD negatively correlated with nonverbal memory decline. BFCS-right amygdala FA correlated with both memory domains, and BFCS-DLPFC MD inversely correlated with memory quotient. Elevated MD in the right Ch4 to ipsilateral hippocampal tracts served as a sensitive imaging biomarker for nonverbal memory impairment.

TLE patients exhibit cognitive and visual-spatial memory deficits, with BFCS tract damage being more pronounced in LTLE and HS patients. The BFCS and its projection fibers demonstrate potential correlations with cognitive function and may be involved in the neural mechanisms of cognitive impairment in TLE.