Mechanisms of cognitive impairment in temporal lobe epilepsy: A systematic review of resting-state functional connectivity studies

Temporal lobe epilepsy is the most common form of focal epilepsy and related cognitive dysfunction impacts significantly on quality of life in patients. Identifying the mechanisms of such impairment would assist in the management and treatment of patients. The study of perturbations in resting-state networks could shed light on this subject. The aim of this systematic review was to synthesize findings on the relationship between aberrant resting-state functional connectivity and cognitive performance in patients with TLE. Literature searches were conducted on Scopus and PubMed electronic databases and 17 relevant articles were extracted, all of which studied the association between resting-state functional connectivity (RSFC) and cognition in adults with TLE. Study findings were synthesized according to methods used to analyze resting-state data, cognitive domains tested, and neuropsychology tasks administered. Results show that increased RSFC in the primary epileptogenic hippocampus, and reduced intra-hemispheric RSFC, are associated with weaker memory performance. In left TLE, memory impairment may be compensated for by bilateral hippocampal connectivity, which is also predictive of better postoperative memory outcomes. In right TLE, memory loss may be compensated for by increased connectivity between the contralateral hippocampus and inferior frontal gyrus. There is also tentative evidence that working memory dysfunction is related to reduced RSFC between the medial frontal-insular parietal network and the medial temporal network, executive dysfunction is related to reduced RSFC between frontal and parietal lobes, and between the frontal lobe and subcortical regions and that language dysfunction is related to reduced RSFC within the left fronto-temporal language network. Multicenter studies could refute or support these findings by enrolling large samples of patients and employing multivariate regression analysis to control for the effects of anatomical disruption, interictal discharges, seizure frequency, medication, and mood. Systematic review registration: PROSPERO: 191323.