Mesial temporal lobe epilepsy (mTLE) affects the brain networks at several levels and patients suffering from mTLE experience cognitive impairment for language and memory. Considering the importance of language and memory reorganization in this condition, the present study explores changes of the embedded languageand-memory network (LMN) in terms of functional connectivity (FC) at rest, as measured with functional MRI. We also evaluate the cognitive efficiency of the reorganization, that is, whether or not the reorganizations support or allow the maintenance of optimal cognitive functioning despite the seizure-related damage.Data from 37 patients presenting unifocal mTLE were analyzed and compared to 48 healthy volunteers in terms of LMN-FC using two methods: pairwise correlations (region of interest [ROI]-to-ROI) and graph theory. The cognitive efficiency of the LMN-FC reorganization was measured using correlations between FC parameters and language and memory scores. Our findings revealed a large perturbation of the LMN hubs in patients. We observed a hyperconnectivity of limbic areas near the dysfunctional hippocampus and mainly a hypoconnectivity for several cortical regions remote from the dysfunctional hippocampus. The loss of FC was more important in left mTLE (L-mTLE) than in right (R-mTLE) patients. The LMN-FC reorganization may not be always compensatory and not always useful for patients as it may be associated with lower cognitive performance. We discuss the different connectivity patterns obtained and conclude that interpretation of FC changes in relation to neuropsychological scores is important to determine cognitive efficiency, suggesting the concept of "connectome" would gain to be associated with a "cognitome" concept. K E Y W O R D S brain plasticity, functional connectivity, graph theory, language, memory, mesial temporal lobe epilepsy, resting-state fMRI

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In the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that “aging-modulating factors” (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF.

Highlights Language and memory interact as a composite function based on the LMN network. LMN configuration is state- and condition-dependent (healthy–pathological). LMN reconfiguration is reflected in network segregation and integration changes. LMN reconfiguration in HC depends on flexibility of key language and memory regions. LMN reconfiguration in TLE shows increased segregation and closer modules.