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The insula is a multiconnected brain region that centralizes a wide range of information, from the most internal bodily states, such as interoception, to high-order processes, such as knowledge about oneself. Therefore, the insula would be a core region involved in the self networks. Over the past decades, the question of the self has been extensively explored, highlighting differences in the descriptions of the various components but also similarities in the global structure of the self. Indeed, most of the researchers consider that the self comprises a phenomenological part and a conceptual part, in the present moment or extending over time. However, the anatomical substrates of the self, and more specifically the link between the insula and the self, remain unclear. We conducted a narrative review to better understand the relationship between the insula and the self and how anatomical and functional damages to the insular cortex can impact the self in various conditions. Our work revealed that the insula is involved in the most primitive levels of the present self and could consequently impact the self extended in time, namely autobiographical memory. Across different pathologies, we propose that insular damage could engender a global collapse of the self.

Background Cortical and subcortical cognitive impairments are usually found in dementia with Lewy bodies (DLB). Roughly, they comprise visuo-constructive/executive function and attention/processing speed impairments, whereas memory would remain relatively spared. In this study, we focused on the neuro-anatomical substrates of attention and processing speed, which is still poorly understood. For the purpose of the study, we examined the correlations between behavioral scores measuring the speed of processing and the degree of cerebral atrophy in patients with prodromal to moderate DLB. Methods Ninety-three prodromal to moderate DLB patients (mean MMSE = 25.5) were selected to participate in the study as well as 28 healthy elderly subjects (mean MMSE = 28.9), matched in terms of age and educational level. The Trail Making Test A (TMTA) and the Digit Symbol Substitution Test (DSST) were used to assess attention and processing speed. Behavioral performances were compared between patients and healthy control subjects. Three-dimensional MRI images were acquired for all participants, and correlational analyses were performed in the patient group using voxel-based morphometry (VBM). Results The behavioral results on both the TMTA ( p  = .026) and the DSST ( p  < .001) showed significantly impaired performances in patients in comparison with control subjects. In addition, correlational analyses using VBM revealed for the TMTA negative correlations in the caudate nucleus (left cluster peak significant at .05 FWE corrected), the putamen, the left thalamus, and the subthalamic nuclei ( p  < .05 FDR corrected). Some positive correlations associated with the DSST were found in the right inferior frontal gyrus, the left thalamus, and the left cerebellum ( p  < .001 uncorrected). Conclusions The behavioral results are in line with the literature on the DLB cognitive profile and confirm the existence of attention and processing speed impairment. Interestingly, VBM analysis revealed the involvement of the basal ganglia, in particular, the left caudate nucleus, which is part of the attention cerebral network, suggesting an important role of this structure for attentional processing speed. This also suggests the clinical implication of damage in this region relatively early in the course of the disease.

Background Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. Methods Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. Results The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. Conclusions Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. Trial registration Clinicaltrials.gov , NCT01926249

Background Dementia with Lewy bodies (DLB) is characterized by insular atrophy, which occurs at the early stage of the disease. Damage to the insula has been associated with disorders reflecting impairments of the most fundamental components of the self, such as anosognosia, which is a frequently reported symptom in patients with Lewy bodies (LB). The purpose of this study was to investigate modifications of the self-concept (SC), another component of the self, and to identify neuroanatomical correlates, in prodromal to mild DLB. Methods Twenty patients with prodromal to mild DLB were selected to participate in this exploratory study along with 20 healthy control subjects matched in terms of age, gender, and level of education. The Twenty Statements Test (TST) was used to assess the SC. Behavioral performances were compared between LB patients and control subjects. Three-dimensional magnetic resonance images (MRI) were acquired for all participants and correlational analyses were performed using voxel-based morphometry (VBM) in whole brain and using a mask for the insula. Results The behavioral results on the TST showed significantly impaired performances in LB patients in comparison with control subjects ( p  < .0001). Correlational analyses using VBM revealed positive correlations between the TST and grey matter volume within insular cortex, right supplementary motor area, bilateral inferior temporal gyri, right inferior frontal gyrus, and left lingual gyrus, using a threshold of p  = .001 uncorrected, including total intracranial volume (TIV), age, and MMSE as nuisance covariates. Additionally, correlational analysis using a mask for the insula revealed positive correlation with grey matter volume within bilateral insular cortex, using a threshold of p  = .005. Conclusions The behavioral results confirm the existence of SC impairments in LB patients from the prodromal stage of the disease, compared to matched healthy controls. As we expected, VBM analyses revealed involvement of the insula, among that of other brain regions, already known to be involved in other self-components. While this study is exploratory, our findings provide important insights regarding the involvement of the insula within the self, confirming the insula as a core region of the self-networks, including for high-order self-representations such as the SC.

Background Dementia with Lewy Bodies (DLB) is responsible for cognitive-behavioural disorders but also for gait disorders. The latter are thought to be related to parkinsonism, but the neural bases of these disorders are not well known, especially in the early stages. The aim of this study was to investigate by volumetric Magnetic Resonance Imaging the neuronal basis of gait disorders in DLB patients, compared to Healthy Elderly Controls and Alzheimer’s Disease patients. Methods Clinical examination with motor assessment including 10-meter walking speed, one-leg balance and Timed Up and Go test, a comprehensive neuropsychological evaluation and 3D brain Magnetic Resonance Imaging were performed on 84 DLB patients, 39 Alzheimer’s Disease patients and 22 Healthy Elderly Controls. We used Statistical Parametric Mapping 12 to perform a one-sample t-test to investigate the correlation between each gait score and gray matter volume ( P  ≤ 0.05 corrected for family-wise error). Results We found a correlation for DLB patients between walking speed and gray matter decrease ( P  < 0.05, corrected for family-wise error) in caudate nuclei, anterior cingulate cortex, mid-cingulate cortex, hippocampi, supplementary motor area, right cerebellar cortex and left parietal operculum. We found no correlation with Timed Up and Go test and one-leg balance. Conclusion Gait disorders are underpinned by certain classical regions such as the cerebellum and the supplementary motor area. Our results suggest there may be a motivational and emotional component of voluntary gait in DLB subjects, underpinned by the cingulate cortex, a spatial orientation component, underpinned by hippocampi and suggest the involvement of brain processing speed and parkinsonism, underpinned by the caudate nuclei. Trial registration The study protocol has been registered on ClinicalTrials.gov. (NCT01876459) on June 12, 2013.

IntroductionSoccer is the most popular sport in the world. This contact sport carries the risk of exposure to repeated head impacts in the form of subconcussions, defined as minimal brain injuries following head impact, with no symptom of concussion. While it has been suggested that exposure to repetitive subconcussive events can result in long-term neurophysiological modifications, and the later development of chronic traumatic encephalopathy, the consequences of these repeated impacts remain controversial and largely unexplored in the context of soccer players.Methods and analysisThis is a prospective, single-centre, exposure/non-exposure, transverse study assessing the MRI and neuropsychological abnormalities in professional retired soccer players exposed to subconcussive impacts, compared with high-level athletes not exposed to head impacts. The primary outcome corresponds to the results of MRI by advanced MRI techniques (diffusion tensor, cerebral perfusion, functional MRI, cerebral volumetry and cortical thickness, spectroscopy, susceptibility imaging). Secondary outcomes are the results of the neuropsychological tests: number of errors and time to complete tests. We hypothesise that repeated subconcussive impacts could lead to morphological lesions and impact on soccer players’ cognitive skills in the long term.Ethics and disseminationEthics approval has been obtained and the study was approved by the Comité de Protection des Personnes (CPP) No 2021-A01169-32. Study findings will be disseminated by publication in a high-impact international journal. Results will be presented at national and international imaging meetings.Trial registration numberNCT04903015.

Background Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage. Methods All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer’s biomarkers (t-Tau, P-Tau, Aβ42, and Aβ40) were also measured. Results The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB. Conclusions The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer’s biomarker does not improve the differential diagnosis between AD and DLB. Trial registration ClinicalTrials.gov, NCT01876459 (AlphaLewyMa)

Background Despite the growing number of discoveries during the past decades about its functions, the insula remains a mysterious ‘island’. In addition to its involvement in basic functions such as gustation and interoception, the insular cortex is now considered a key region for integrated functions such as emotion/motivation processing, decision-making and self-consciousness. We hypothesized that this structure, standing at the crossroads of such functions, could ground personal tastes in general, beyond food preferences and aesthetic judgements. Given that dementia with Lewy bodies is characterized by a focal atrophy within the insular cortex from the early stages, this condition provides an opportunity to test such a hypothesis. Methods We developed a questionnaire to assess potential changes in personal tastes, submitted it to a cohort of 23 patients with early-stage dementia with Lewy bodies and compared their questionnaire results to those of 20 age-matched healthy controls. Furthermore, we performed a global and regional neuroimaging study to test for a potential correlation between the patients’ scores for changes in personal tastes and their insular cortex volumes. Results Our results indicate that the patients presented significant changes in personal tastes compared to the controls, in both food and non-food domains. Moreover, imaging analyses confirmed the involvement of the insular cortex atrophy in the changes in personal tastes using global analysis, and in both food and non-food domains using regional analysis. Conclusions These results bring new insights into the role of the insula as a ‘grey matter of tastes’, this structure supporting personal preferences in general, beyond the food domain. The insular cortex could be involved through its role in motivational processes by the representation of subjective awareness of bodily states during the phenomenological experience of stimulus appraisal. However, we also argue that it could support the abstract representations of personal tastes as self-concepts, acutely exemplifying embodied cognition. Finally, the questionnaire on changes in tastes could constitute an interesting tool to help early diagnosis of dementia with Lewy bodies and to assess insular dysfunction more generally.

INTRODUCTION The cognitive and neuroimaging evolution during dementia with Lewy bodies (DLB) from the prodromal phase (Pro‐DLB; subjective cognitive impairment [SCI] to mild cognitive impairment [MCI]) according to amyloid beta (Aβ) status is poorly understood. METHODS The decline of Lewy‐Memento patients with SCI or MCI was compared according to Aβ status across four groups: Pro‐DLB, prodromal Alzheimer's disease (Pro‐AD), Pro‐DLB+AD, and a group without prodromal DLB and AD (no symptoms [NS]). We observed the evolution of cognitive, functional, quality of life measures, brain volumetry, and metabolism on fluorodeoxyglucose positron emission tomography. RESULTS In the Pro‐DLB and Pro‐DLB+AD groups, Aβ+ patients had more cognitive and functional decline than the Aβ– patients. In the Pro‐AD and NS groups, Aβ+ patients had more functional decline. Aβ+ Pro‐AD showed a greater volume decline of the brain (left insula). DISCUSSION The presence of amyloid lesions worsens very prodromal DLB patients over time, both cognitively and functionally, but without increasing atrophy. Highlights Patients at a very prodromal stage, subjective cognitive impairment or mild cognitive impairment, had a clinical diagnosis of either prodromal Alzheimer's disease (Pro‐AD), prodromal dementia with Lewy bodies (Pro‐DLB), Pro‐DLB+AD, or no diagnosis. Amyloid beta positive (Aβ+) patients had more functional decline, whatever the group. Aβ+ DLB patients (Pro‐DLB and Pro‐DLB+AD) had more global cognitive (Mini‐Mental State Examination) decline. Aβ+ Pro‐AD patients showed a greater volume decline of the left insula.

According to the Construction-Integration model (Kintsch 1988 ; Kintsch 1998 ), two forms of representation are activated during the reading and the comprehension of a text: 1) the text base, which includes semantic propositions and 2) the situation model, corresponding to the integration of the information contained in the text to the memories and knowledge of the reader. Functional neuroimaging studies in healthy subjects have shown that the text base is underpinned by frontal regions and lateral temporal regions whereas the situation model would rather depend on the posterior cingulate cortex, the precuneus and other regions depending on the dimension studied. However, the brain regions highlighted so far were only involved in comprehension and not necessary for this cognitive ability. For the first time, we explored the brain structures necessary to understand texts using a combined VBM/DTI approach in neuropsychological patients with whom we obtained comprehension scores (text base and situation model) after the reading of narrative texts. To our great surprise and contrary to our hypotheses, which were based on the results of functional neuroimaging studies, our own results show that it is the hippocampal region that is necessary to activate and memorize/remember the text base and the situation model. The highlighting of a link between the integrity of a portion of the uncinate fasciculus which is well known to play a role in semantic processing and the performance scores of the text base suggests that the hippocampal region is necessary not only for the retrieval of the text base and of the situation model thanks to episodic memory, but also for the activation of the text base during the reading and the comprehension of a text.