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Objectives: Extra-motor manifestations occur in 50% of patients with amyotrophic lateral sclerosis (ALS). These mainly concern cognition, emotional processing and behavior. Depression and anxiety are less frequent. Little is known about how these manifestations change as the disease progresses. Similarly, although cortical thinning has been well-documented at disease onset, there are scant data about cortical thinning over time and how this correlates with extra-motor manifestations. The present study therefore assessed cognitive, emotional and psychological state and cortical thinning in a group of patients with ALS at baseline and after a follow-up period. Methods: We assessed executive functions, facial emotion recognition, depressive and anxious symptoms, and cortical thinning in 43 patients with ALS at baseline, comparing them with 28 healthy controls, and 21 of them 9 months later. We looked for links among the extra-motor manifestations and correlations with cortical thickness. Results: At baseline, patients had poor executive function and recognition of complex emotions from the eyes, and more anxious and depressive symptoms than controls. At follow-up, only inhibition abilities had worsened. Cortical thinning was observed in bilateral pre-central regions and other parts of the cerebral cortex at baseline. Over time, it worsened in motor and extra-motor areas. Executive functions correlated with thinning in the middle and inferior frontal gyrus and orbitofrontal cortex. Conclusions: During follow-up, there was little deterioration in extra-motor manifestations and psychological state, despite continuing cortical thinning. Patients with affective Theory of Mind (ToM) changes seemed less depressed than the others. Impaired mental flexibility was subtended by prefrontal regions with cortical thinning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Benbrika, Doidy, Carluer, Mondou, Pélerin, Eustache, Viader and Desgranges.)

Introduction: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes progressive and extensive motor deficits. Patients may also have cognitive impairments or alteration of emotional processing. Very few studies, however, have looked at deficits in how they experience their own feelings (alexithymia). Methods: We assessed alexithymia in 28 patients with ALS using the 20-item Toronto Alexithymia Scale (TAS-20), comparing them with a control group matched for sex, age, and education level. We took into account both the total score of the TAS-20 and its three subscores corresponding to the three dimensions of alexithymia: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Patients also underwent a neuropsychological assessment and anatomical magnetic resonance imaging (MRI) in order to correlate cognitive performances and gray matter volume and level of alexithymia. Results: On average, ALS subjects had a significantly higher total score and DIF sub-score of the TAS-20 than controls indicating an increased alexithymia in patients. Total and DIF Scores correlated significantly and negatively to gray matter volume of the prefrontal cortex, right superior temporal pole and parahippocampal gyri. No correlations were found between scores on executive functions and those on the TAS-20. Conclusion: The first stage of one's own emotional processing seems to be affected in ALS independently of executive dysfunction. This trouble seems to be underpinned by cerebral regions that are well known to be both implicated in alexithymia in healthy subjects and altered in ALS.

Encoding and retrieval processes in memory for pairs of pictures are thought to be influenced by inter-item similarity and by features of individual items. Using Event-Related Potentials (ERP), we aimed to identify how these processes impact on both the early mid-frontal FN400 and the Late Positive Component (LPC) potentials during associative retrieval of pictures. Twenty young adults undertook a sham task, using an incidental encoding of semantically related and unrelated pairs of drawings. At test, we conducted a recognition task in which participants were asked to identify target identical pairs of pictures, which could be semantically related or unrelated, among new and rearranged pairs. We observed semantic (related and unrelated pairs) and condition effects (old, rearranged and new pairs) on the early mid-frontal potential. First, a lower amplitude was shown for identical and rearranged semantically related pairs, which might reflect a retrieval process driven by semantic cues. Second, among semantically unrelated pairs, we found a larger negativity for identical pairs, compared to rearranged and new ones, suggesting additional retrieval processing that focuses on associative information. We also observed an LPC old/new effect with a mid-parietal and a right occipito-parietal topography for semantically related and unrelated old pairs, demonstrating a recollection phenomenon irrespective of the degree of association. These findings suggest that associative recognition using visual stimuli begins at early stages of retrieval, and differs according to the degree of semantic relatedness among items. However, either strategy may ultimately lead to recollection processes.

Memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, termed memory consolidation. Numerous data indicate that sleep plays a major role in this process, notably due to the specific neurochemical environment and the electrophysiological activity observed during the night. Two putative, probably not exclusive, models ("hippocampo-neocortical dialogue" and "synaptic homeostasis hypothesis") have been proposed to explain the beneficial effect of sleep on memory processes. However, all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults. This review outlines the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.