Effects of sleep disturbances and circadian rhythms modifications on cognition in breast cancer women before and after adjuvant chemotherapy: the ICANSLEEP-1 protocol.

BACKGROUND: Many patients treated for breast cancer (BC) complain about cognitive difficulties affecting their daily lives. Recently, sleep disturbances and circadian rhythm disruptions have been brought to the fore as potential contributors to cognitive difficulties in patients with BC. Yet, studies on these factors as well as their neural correlates are scarce. The purpose of the ICANSLEEP-1 (Impact of SLEEP disturbances in CANcer) study is to characterize sleep using polysomnography and its relationship with the evolution of cognitive functioning at both the behavioral and the neuroanatomical levels across treatment in BC patients treated or not with adjuvant chemotherapy. METHODS: ICANSLEEP-1 is a longitudinal study including BC patients treated with adjuvant chemotherapy (n = 25) or not treated with adjuvant chemotherapy (n = 25) and healthy controls with no history of BC (n = 25) matched for age (45-65 years old) and education level. The evaluations will take place within 6 weeks after inclusion, before the initiation of chemotherapy (for BC patients who are candidates for chemotherapy) or before the first fraction of radiotherapy (for BC patients with no indication for chemotherapy) and 6 months later (corresponding to 2 weeks after the end of chemotherapy). Episodic memory, executive functions, psychological factors, and quality of life will be assessed with validated neuropsychological tests and self-questionnaires. Sleep quantity and quality will be assessed with polysomnography and circadian rhythms with both actigraphy and saliva cortisol. Grey and white matter volumes, as well as white matter microstructural integrity, will be compared across time between patients and controls and will serve to further investigate the relationship between sleep disturbances and cognitive decline. DISCUSSION: Our results will help patients and clinicians to better understand sleep disturbances in BC and their relationship with cognitive functioning across treatment. This will aid the identification of more appropriate sleep therapeutic approaches adapted to BC patients. Improving sleep in BC would eventually help limit cognitive deficits and thus improve quality of life during and after treatments. TRIAL REGISTRATION: NCT05414357, registered June 10, 2022. PROTOCOL VERSION: Version 1.2 dated March 23, 2022.

[Genetics of amyotrophic lateral sclerosis]. / Génétique de la sclérose latérale amyotrophique.

GENETICS OF AMYOTROPHIC LATERAL SCLEROSIS. Approximately 10 to 15% of people with amyotrophic lateral sclerosis (ALS) have a family history of the disease. In 2/3 of them, but also in 10% of subjects without any family history of ALS, a pathogenic genetic variant can be identified. Many genes are involved, the four main ones being C9orf72 (which can also be responsible for dementia), SOD1, TARDBP and FUS. ALS of genetic origin is almost always inherited in an autosomal dominant pattern. The progress made in recent years in the knowledge of the genetic forms of ALS has led to a better understanding of the pathophysiology of the disease and has opened up new therapeutic avenues, some of which are already being explored. For all these reasons, it is now recommended that all patients with ALS, whether familial or not, undergo a genetic investigation, with analyses appropriate to their age and family history. When a pathogenic variant is found, it can then be sought in at-risk relatives who so desire. These tests must follow legally mandated procedures and can only be conducted in a specialized ALS center under the supervision of a geneticist after a thorough discussion of the personal and family implications of the result and written consent from the patient.

GÉNÉTIQUE DE LA SCLÉROSE LATÉRALE AMYOTROPHIQUE. Environ 10 à 15 % des sujets atteints de sclérose latérale amyotrophique (SLA) ont des antécédents familiaux. Chez les deux tiers d'entre eux, mais aussi chez 10 % des sujets sans aucun antécédent familial de SLA, un variant génétique pathogène peut être mis en évidence. De nombreux gènes sont concernés, les quatre principaux étant C9orf72 (qui peut également être responsable d'une démence), SOD1, TARDBP et FUS . La SLA d'origine génétique se transmet pratiquement toujours selon une hérédité autosomique dominante. Les progrès accomplis ces dernières années dans la connaissance des formes génétiques de SLA permettent de mieux connaître la physiopathologie de la maladie et ouvrent de nouvelles pistes thérapeutiques dont certaines sont déjà en cours d'exploration. Pour toutes ces raisons, il est aujourd'hui recommandé, chez tout sujet atteint de SLA, familiale ou non, d'entreprendre une enquête génétique, avec des analyses appropriées à l'âge et aux antécédents familiaux. Lorsqu'un variant pathogène est trouvé, il peut alors être recherché chez les apparentés à risque qui le souhaitent. Ces analyses doivent respecter des procédures encadrées par la loi, et ne peuvent être conduites que dans un centre spécialisé pour la prise en charge de la SLA, et sous la responsabilité d'un généticien, après une discussion approfondie sur les implications personnelles et familiales du résultat, et le consentement écrit du patient.

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. Methods: This prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. Results: Two hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 µg/L [520-2075] vs 1220 µg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. Conclusion: Two widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

Disruption in normal correlational patterns of metabolic networks in the limbic circuit during transient global amnesia.

Transient global amnesia is characterized by the sudden apparition of severe episodic amnesia, mainly anterograde, associated with emotional changes. Even though the symptoms are stereotyped, cerebral mechanism underlying transient global amnesia remains unexplained and previous studies using positron emission tomography do not show any clear results or consensus on cerebral regions impacted during transient global amnesia. This study included a group of 10 transient global amnesic patients who underwent 18F-fluorodeoxyglucose positron emission tomography during the acute or recovery phase of the episode and 10 paired healthy controls. Episodic memory was evaluated with the encoding-storage-retrieval paradigm and a story recall test of the Wechsler's memory scale and anxiety was assessed with the Spielberger scale. We used statistical parametric mapping to identify modifications of whole-brain metabolism. Regarding hypometabolism, there was no brain region systematically affected in all transient global amnesic patients and the comparison between amnesic patients and controls did not show any significant differences. To better understand the specific implication of the limbic circuit in the pathophysiology of transient global amnesia, we then conducted a correlational analysis that included regions of this network. Our findings showed that in healthy controls, regions of the limbic circuit seem to operate in a synchronized way with all regions being highly correlated to each other. On the opposite, in transient global amnesic patients, we observed a clear disruption of this normal correlational patterns between regions with the medial temporal lobe (the hippocampus, parahippocampal gyrus and amygdala) included in one cluster and the orbitofrontal cortex, anterior and posterior cingulate gyrus and thalamus gathered in the other one. Given the individual variability in the time course of transient global amnesia, the direct comparison between a group of patients and controls does not seem to favour the identification of subtle and transient alterations in regional metabolism. The involvement of an extended network, such as the limbic circuit, seems more likely to explain the symptoms of patients. Indeed, the synchronization of regions within the limbic circuit seems to be altered during transient global amnesia, which could explain the amnesia and anxiety observed in transient global amnesic patients. The present study thus deepens our understanding of the mechanisms underlying not only amnesia but also the emotional component of transient global amnesia by considering it as a disruption in the normal correlational patterns within the limbic circuit.

Attentional capture mediates the emergence and suppression of intrusive memories.

Intrusive memories hijack consciousness and their control may lead to forgetting. However, the contribution of reflexive attention to qualifying a memory signal as interfering is unknown. We used machine learning to decode the brain's electrical activity and pinpoint the otherwise hidden emergence of intrusive memories reported during a memory suppression task. Importantly, the algorithm was trained on an independent attentional model of visual activity, mimicking either the abrupt and interfering appearance of visual scenes into conscious awareness or their deliberate exploration. Intrusion of memories into conscious awareness were decoded above chance. The decoding accuracy increased when the algorithm was trained using a model of reflexive attention. Conscious detection of intrusive activity decoded from the brain signal was central to the future silencing of suppressed memories and later forgetting. Unwanted memories require the reflexive orienting of attention and access to consciousness to be suppressed effectively by inhibitory control.

Sleep-dependent memory consolidation in breast cancer: Use of a virtual reality prospective memory task.

Background: Previous studies have revealed both sleep alterations and prospective memory (PM) impairments in breast cancer (BC) patients. PM refers to memory of intended actions and is crucial for daily living tasks and treatment compliance. As sleep is known to favor memory consolidation, one may expect that changes in sleep quality related to BC would have an impact on PM performance. This study aimed at assessing sleep-dependent consolidation of intentions using an ecological, virtual reality-based PM task in BC patients not treated with chemotherapy. Materials and methods: Thirty-seven early stages BC patients and 21 healthy controls (HC) participated in this study. PM was assessed using a virtual reality task, during which participants learnt a list of intentions and recalled them after a retention interval filled with a day awake or a night of sleep monitored by polysomnography. Sleep spindles and slow waves, brain oscillations involved in sleep-dependent memory consolidation, were quantified automatically using the Aseega software (Physip). Subjective sleep disturbances and markers of quality of life (psychological distress, fatigue, and well-being) were assessed by questionnaires. Results: Greater PM performance was observed after sleep than after an equivalent period of daytime wakefulness for both groups (HC and BC). PM performance after sleep did not differ significantly between groups. Yet, BC patients reported greater sleep disturbances than HC which were related with poorer intentions retrieval, greater psychological distress, fatigue and poorer well-being. The frequency of spindles was higher and the amplitude of slow waves lower in BC patients compared to HC. However, no significant association was observed between polysomnography parameters and PM scores in the whole sample of participants. Conclusion: Although subtle changes in brain oscillations involved in sleep-dependent memory consolidation were observed, these changes did not significantly impair overnight PM consolidation in BC patients. Nevertheless, poorer PM performance was associated with greater sleep complaints which in turn were related to poorer quality of life. Overall, these data suggest that sleep-dependent PM consolidation mechanisms are not altered in early stages BC patients not treated with chemotherapy. Further investigations are needed to understand the association between markers of quality of life and sleep-dependent memory consolidation.

Longitudinal grey matter and metabolic contributions to cognitive changes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is characterized by rapidly evolving cognitive and brain impairments. While previous work revealed structural and functional alterations associated with cognitive decline in patients suffering from amyotrophic lateral sclerosis, the relationships between anatomo-functional changes and both disease's progression and the evolution of cognitive performance remain largely unexplored. Here, we took advantage of repeated multi-modal acquisitions in patients with amyotrophic lateral sclerosis over 1 year to assess the longitudinal sequence of grey matter atrophy, glucose metabolism and cognitive changes. Results revealed metabolic and structural changes over frontal, thalamic and temporal regions. Both cortical hypermetabolism and hypometabolism (right temporal gyrus and right angular gyrus, respectively) were associated with cognitive performance and thalamic hypometabolism during the follow-up testing session. Furthermore, the inferior frontal gyrus atrophy mediated the relation between early hypometabolism in this region and the subsequent decline of the theory of mind abilities. Marked volume loss was associated with larger hypometabolism and impaired cognitive performance. To our knowledge, this is the first study to longitudinally examine both grey matter volume and metabolic alteration patterns in patients with amyotrophic lateral sclerosis, over a mean follow-up time of 1 year. We identify how changes of the inferior frontal gyrus critically underly later cognitive performance, shedding new light on its high prognostic significance for amyotrophic lateral sclerosis-related changes. These results have important implications for our understanding of structural and functional changes associated with amyotrophic lateral sclerosis and how they underly cognitive impairments.

Altered predictive control during memory suppression in PTSD.

Aberrant predictions of future threat lead to maladaptive avoidance in individuals with post-traumatic stress disorder (PTSD). How this disruption in prediction influences the control of memory states orchestrated by the dorsolateral prefrontal cortex is unknown. We combined computational modeling and brain connectivity analyses to reveal how individuals exposed and nonexposed to the 2015 Paris terrorist attacks formed and controlled beliefs about future intrusive re-experiencing implemented in the laboratory during a memory suppression task. Exposed individuals with PTSD used beliefs excessively to control hippocampal activity during the task. When this predictive control failed, the prediction-error associated with unwanted intrusions was poorly downregulated by reactive mechanisms. This imbalance was linked to higher severity of avoidance symptoms, but not to general disturbances such as anxiety or negative affect. Conversely, trauma-exposed participants without PTSD and nonexposed individuals were able to optimally balance predictive and reactive control during the memory suppression task. These findings highlight a potential pathological mechanism occurring in individuals with PTSD rooted in the relationship between the brain's predictive and control mechanisms.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

Rest activity rhythms characteristics of breast cancer women following endocrine therapy.

Rest-activity rhythm (RAR) disruptions are frequently associated with chemotherapy in breast cancer (BC), but they are less known in BC with endocrine therapy (ET). The aim of this ancillary study was to characterize the RAR and estimated sleep characteristics from actigraphy in BC patients either treated (ET+) or untreated with ET (ET-), compared to healthy controls (HC) and using a cross-sectional design. Eighteen ET+, 18 ET-, and 16 HC completed questionnaires and wore wrist actigraphs at home for 2 weeks. Parametric and nonparametric RAR, sleep parameters, and quality of life were compared between groups (p < .05). BC groups presented lower daytime activity than HC according to RAR analysis (mesor and M10 parameters). Compared to HC, ET- had lower inter-daily stability and ET+ had greater sleep complaints. Compared to ET-, ET+ had lower sleep efficiency, more time awake, and higher activity levels at night, as assessed with actigraphy. Our results suggest an effect of cancer independent of treatment on RAR in BC, highlighting the need for further investigation of this topic. In contrast, sleep as assessed with actigraphy seems modified only during ET which matches with patients' sleep complaints. Further longitudinal studies would aid in confirming the latter hypothesis.

Episodic Autobiographical Memory Impairment and Differences in Pronoun Use: Study of Self-Awareness in Functional Amnesia and Transient Global Amnesia.

The subjective experience associated to memory processing is the core of the definition of episodic autobiographical memory (EAM). However, while it is widely known that amnesia affects the content of memories, few studies focused on the consequences of an impairment of EAM on the subjective self, also called the I-self. In the present study, we explored the I-self in two puzzling disorders that affect EAM: functional amnesia, which has an impact on autobiographical memory, and transient global amnesia (TGA), which only affects episodic memory. I-self was assessed through an original measure of self-integration in autobiographical narratives, namely the use of general or personal pronouns. Results showed that patients with functional amnesia tended to use general pronouns, whereas patients with TGA preferentially used the first person. The link between I-self and depersonalization-derealisation tendencies was also explored, showing dissociative tendencies in patients with functional amnesia but not in patients with TGA. We discuss these results from a combined neuropsychological and psychopathological perspective, with a view to proposing an explanatory model of the links between self-awareness and the episodic component of autobiographical memory.

Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)-Comparison With ISCVT Cohort.

Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown. Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort. Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al. Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients. Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.

Longitudinal Study of Cognitive and Emotional Alterations in Amyotrophic Lateral Sclerosis: Clinical and Imaging Data.

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.

Variations in response to trauma and hippocampal subfield changes.

Models of posttraumatic stress disorder (PTSD) suggest that the hippocampus is key to the persistence of traumatic memory. Yet very little is known about the precise changes that take place in this structure, nor their relation with PTSD symptoms. Previous studies have mostly used magnetic resonance imaging (MRI) at low resolutions, making it impossible to identify sensitive anatomical landmarks, or compared groups often unequally matched in terms of traumatic exposure. The present cross-sectional study included 92 individuals who had all been exposed to the terrorist attacks in Paris on November 13, 2015 (53 of whom subsequently developed PTSD) and 56 individuals who had not been exposed. Hippocampal subfield volumes were estimated using cross-validated automatic segmentation of high-resolution MRI images. Results revealed changes in CA1 and CA2-3/dentate gyrus (DG) volumes in individuals with PTSD, but not in resilient (i.e., exposed but without PTSD) individuals, after controlling for potential nuisance variables such as previous traumatic exposure and substance abuse. In line with current models of hippocampal subfield functions, CA1 changes were linked to the uncontrollable re-experiencing of intrusive memories, while CA2-3/DG changes, potentially exacerbated by comorbid depression, fostered the overgeneralization of fear linked to avoidance and hypervigilance behaviors. Additional analyses revealed that CA1 integrity was linked to optimum functioning of the memory control network in resilient individuals. These findings shed new light on potential pathophysiological mechanisms in the hippocampus subtending the development of PTSD and the failure to recover from trauma.

Self-awareness in Transient Global Amnesia: distinguishing the effects of transient memory disorder vs. pre-existing vulnerability factors.

Numerous evidences suggest the existence of relationships between the impairment of episodic memory, acute stress exposure and variations in self-awareness (SA). Here, we examined 27 patients presenting transient global amnesia (TGA), a clinical condition which combines episodic amnesia and high anxiety, thanks to state and trait questionnaires of SA. We observed variation of SA depending on the stage of TGA (acute, recovery and follow-up). We also found preexisting differences in patient's awareness of their own image when the precipitating event was physical, encouraging us to give more consideration to the social determinants of stress in physiological cascade of TGA.

Effect of familial clustering in the genetic screening of 235 French ALS families.

OBJECTIVES: To determine whether the familial clustering of amyotrophic lateral sclerosis (ALS) cases and the phenotype of the disease may help identify the pathogenic genes involved. METHODS: We conducted a targeted next-generation sequencing analysis on 235 French familial ALS (FALS), unrelated probands to identify mutations in 30 genes linked to the disease. The genealogy, that is, number of cases and generations with ALS, gender, age, site of onset and the duration of the disease were analysed. RESULTS: Regarding the number of generations, 49 pedigrees had only one affected generation, 152 had two affected generations and 34 had at least three affected generations. Among the 149 pedigrees (63.4%) for which a deleterious variant was found, an abnormal G4C2 expansion in C9orf72 was found in 98 cases as well as SOD1, TARBP or FUS mutations in 30, 9 and 7 cases, respectively. Considering pedigrees from the number of generations, abnormal G4C2 expansion in C9orf72 was more frequent in pedigrees with pairs of affected ALS cases, which represented 65.2% of our cohort. SOD1 mutation involved all types of pedigrees. No TARDBP nor FUS mutation was present in monogenerational pedigrees. TARDBP mutation predominated in bigenerational pedigrees with at least three cases and FUS mutation in multigenerational pedigrees with more than seven cases, on average, and with an age of onset younger than 45 years. CONCLUSION: Our results suggest that familial clustering, phenotypes and genotypes are interconnected in FALS, and thus it might be possible to target the genetic screening from the familial architecture and the phenotype of ALS cases.

Long-term modulation of cardiac activity induced by inhibitory control over emotional memories.

Efforts to exclude past experiences from conscious awareness can lead to forgetting. Memory suppression is central to affective disorders, but we still do not really know whether emotions, including their physiological causes, are also impacted by this process in normal functioning individuals. In two studies, we measured the after-effects of suppressing negative memories on cardiac response in healthy participants. Results of Study 1 revealed that efficient control of memories was associated with long-term inhibition of the cardiac deceleration that is normally induced by disgusting stimuli. Attempts to suppress sad memories, by contrast, aggravated the cardiac response, an effect that was closely related to the inability to forget this specific material. In Study 2, electroencephalography revealed a reduction in power in the theta (3-8 Hz), alpha (8-12 Hz) and low-beta (13-20 Hz) bands during the suppression of unwanted memories, compared with their voluntary recall. Interestingly, however, the reduction of power in the theta frequency band during memory control was related to a subsequent inhibition of the cardiac response. These results provide a neurophysiological basis for the influence of memory control mechanisms on the cardiac system, opening up new avenues and questions for treating intrusive memories using motivated forgetting.