The dendritic ERGIC: Microtubule and actin cytoskeletons participate in stop-and-go movement of mobile carriers between stable structures.

The endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) is a membranous organelle that mediates protein transport between the ER and the Golgi apparatus. In neurons, clusters of these vesiculotubular structures are situated throughout the cell in proximity to the ER, passing cargo to the cis-Golgi cisternae, located mainly in the perinuclear region. Although ERGIC markers have been identified in neurons, the distribution and dynamics of neuronal ERGIC structures have not been characterized yet. Here, we show that long-distance ERGIC transport occurs via an intermittent mechanism in dendrites, with mobile elements moving between stationary structures. Slow and fast live-cell imaging have captured stable ERGIC structures remaining in place over long periods of time, as well as mobile ERGIC structures advancing very short distances along dendrites. These short distances have been consistent with the lengths between the stationary ERGIC structures. Kymography revealed ERGIC elements that moved intermittently, emerging from and fusing with stationary ERGIC structures. Interestingly, this movement apparently depends not only on the integrity of the microtubule cytoskeleton, as previously reported, but on the actin cytoskeleton as well. Our results indicate that the dendritic ERGIC has a dual nature, with both stationary and mobile structures. The neural ERGIC network transports proteins via a stop-and-go movement in which both the microtubule and the actin cytoskeletons participate.

RyR-mediated Ca2+ release elicited by neuronal activity induces nuclear Ca2+ signals, CREB phosphorylation, and Npas4/RyR2 expression.

The expression of several hippocampal genes implicated in learning and memory processes requires that Ca2+ signals generated in dendritic spines, dendrites, or the soma in response to neuronal stimulation reach the nucleus. The diffusion of Ca2+ in the cytoplasm is highly restricted, so neurons must use other mechanisms to propagate Ca2+ signals to the nucleus. Here, we present evidence showing that Ca2+ release mediated by the ryanodine receptor (RyR) channel type-2 isoform (RyR2) contributes to the generation of nuclear Ca2+ signals induced by gabazine (GBZ) addition, glutamate uncaging in the dendrites, or high-frequency field stimulation of primary hippocampal neurons. Additionally, GBZ treatment significantly increased cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation-a key event in synaptic plasticity and hippocampal memory-and enhanced the expression of Neuronal Per Arnt Sim domain protein 4 (Npas4) and RyR2, two central regulators of these processes. Suppression of RyR-mediated Ca2+ release with ryanodine significantly reduced the increase in CREB phosphorylation and the enhanced Npas4 and RyR2 expression induced by GBZ. We propose that RyR-mediated Ca2+ release induced by neuronal activity, through its contribution to the sequential generation of nuclear Ca2+ signals, CREB phosphorylation, Npas4, and RyR2 up-regulation, plays a central role in hippocampal synaptic plasticity and memory processes.

VolumePeeler: a novel FIJI plugin for geometric tissue peeling to improve visualization and quantification of 3D image stacks.

MOTIVATION: Quantitative descriptions of multi-cellular structures from optical microscopy imaging are prime to understand the variety of three-dimensional (3D) shapes in living organisms. Experimental models of vertebrates, invertebrates and plants, such as zebrafish, killifish, Drosophila or Marchantia, mainly comprise multilayer tissues, and even if microscopes can reach the needed depth, their geometry hinders the selection and subsequent analysis of the optical volumes of interest. Computational tools to "peel" tissues by removing specific layers and reducing 3D volume into planar images, can critically improve visualization and analysis. RESULTS: We developed VolumePeeler, a versatile FIJI plugin for virtual 3D "peeling" of image stacks. The plugin implements spherical and spline surface projections. We applied VolumePeeler to perform peeling in 3D images of spherical embryos, as well as non-spherical tissue layers. The produced images improve the 3D volume visualization and enable analysis and quantification of geometrically challenging microscopy datasets. AVAILABILITY: ImageJ/FIJI software, source code, examples, and tutorials are openly available in https://cimt.uchile.cl/mcerda.

Altered neural control of gait and its association with pain and joint impairment in adults with haemophilic arthropathy: Clinical and methodological implications.

INTRODUCTION: It is unknown whether altered neural control is associated with clinical outcomes in people with haemophilic arthropathy (PWHA). The dynamic motor control index during walking (Walk-DMC) is a summary metric of neural control. AIMS: The primary aim of this study was to apply the Walk-DMC to assess if people diagnosed with haemophilic arthropathy have impaired neural control of gait and investigate the association of Walk-DMC with pain and joint impairment. METHOD: The Walk-DMC was assessed using surface electromyography in 11 leg muscles. Twenty-two PWHA and 15 healthy subjects walked on a 30-m walkway at 1 m/s. In addition, pain (visual analogue scale), knee flexion contracture (degrees) and joint impairment (Haemophilia Joint Health Score, HJHS) were assessed. The clinical outcomes were correlated with the Walk-DMC. Multiple regression analysis was performed to predict the Walk-DMC using the clinical outcomes. RESULTS: In 13 PWHA the Walk-DMC was beyond the normal range (80-120 pts). PWHA with an altered Walk-DMC showed more years with arthropathy, more pain, higher knee flexion contracture and a higher HJHS score (P < .05, effect size > .8). Significant negative moderate associations between Walk-DMC and pain, knee flexion contracture and HJHS were found (P < .05). The model that best predicted the Walk-DMC was the pain with knee flexion contracture (R2  = .44; P = .004). CONCLUSIONS: PWHA with abnormal neural control of gait also has more years with arthropathy, more pain, and more impaired joints. Our results indicate an association between the Walk-DMC index and joint damage, specifically with pain in combination with knee flexion contracture.

Modular reorganization of gait in chronic but not in artificial knee joint constraint.

It is currently unknown if modular reorganization does occur if not the central nervous system, but the musculoskeletal system is affected. The aims of this study were to investigate 1) the effects of an artificial knee joint constraint on the modular organization of gait in healthy subjects; and 2) the differences in modular organization between healthy subjects with an artificial knee joint constraint and people with a similar but chronic knee joint constraint. Eleven healthy subjects and eight people with a chronic knee joint constraint walked overground at 1 m/s. The healthy subjects also walked with a constraint limiting knee joint movement to 20°. The total variance accounted (tVAF) for one to four synergies and modular organization were assessed using surface electromyography from 11 leg muscles. The distribution of number of synergies were not significantly different between groups. The tVAF and the motor modules were not significantly affected by the artificial knee constraint. A higher tVAF for one and two synergies, as well as merging of motor modules were observed in the chronic knee constraint group. We conclude that in the short-term a knee constraint does not affect the modular organization of gait, but in the long-term a knee constraint results in modular reorganization. These results indicate that merging of motor modules may also occur when changes in the mechanics of the musculoskeletal system is the primary cause of the motor impairment.NEW & NOTEWORTHY It is currently unknown if modular reorganization does occur if not the central nervous system, but the musculoskeletal system is affected. This study showed that in the short-term a knee constraint does not affect the modular organization of gait, but in the long-term a knee constraint results in modular reorganization. These results indicate that modular reorganization may also occur when changes in the mechanics of the musculoskeletal system is the primary cause of the motor impairment.

Qualitative ultrasonography scale of the intensity of local twitch response during dry needling and its association with modified joint range of motion: a cross-sectional study.

BACKGROUND: The relevance of local twitch response (LTR) during dry needling technique (DNT) is controversial, and it is questioned whether LTR is necessary for successful outcomes. Furthermore, because the LTR during the deep DNT may be evoked with different intensities, it is unknown whether the magnitude of LTR intensity is associated with optimal clinical results, especially concerning to the effects of joint maximal range of motion (ROM). This study aimed to (i) determine whether visual inspections can quantify the LTR intensity during the DNT through a qualitative ultrasonography scale of LTR intensity (US-LTR scale), and (ii) assess the differences of US-LTR scale associated with changes in the maximal joint ROM. METHODS: Using a cross-sectional design, seven asymptomatic individuals were treated with DNT in the latent myofascial trigger point in both medial gastrocnemius muscles. During DNT, three consecutive LTRs were collected. The US-LTR scale was used to classify the LTRs into strong, medium, and weak intensities. The categories of US-LTR were differentiated by the velocity of LTRs using the optical flow algorithm. ROM changes in ankle dorsiflexion and knee extension were assessed before and immediately after DNT. RESULTS: The US-LTR scale showed the third LTR was significantly smaller than the first one (p < 0.05). A significant difference in velocity was observed between US-LTR categories (p < 0.001). A significant difference in the ROM was observed between the strong and weak-medium intensity (p < 0.05). CONCLUSIONS: The present findings suggest that the LTR intensity can be assessed using a qualitative US-LTR scale, and the effects of DNT on joint maximal ROM is maximized with higher LTR intensity. This study reports a novel qualitative method for LTR analysis with potential applications in research and clinical settings. However, further research is needed to achieve a broader application.

Is Biceps Femoris Aponeurosis Size an Independent Risk Factor for Strain Injury?

This study examined whether professional footballers with previous biceps femoris long head (BFLH) injury in the last 3-years present a smaller proximal aponeurosis (Apo-BFLH) size compared to footballers with no previous injury. We examined the Apo-BFLH and BFLH size using magnetic resonance imaging and tested the knee flexor maximal isometric strength in 80 thighs of 40 footballers. Apo-BFLH size parameters were processed using a semi-automated procedure. Outcomes were compared between thighs with (n=9) vs. without (n=71) previous BFLH injury. No differences were observed between injured and non-injured thighs for the Apo-BFLH and BFLH size parameters (p>0.05) except for Apo-BFLH volume, which was higher in the non-injured thighs of athletes with previous injury (3692.1±2638.4 mm3, p<0.006) compared to the left (2274.1±798.7 mm3) thighs of athletes without previous injury. A higher knee flexor isometric strength was observed in the injured limb of athletes with previous BFLH injury (196.5±31.9 Nm, p<0.003) compared to the left (156.2±31.4 Nm) and right (160.0±31.4 Nm) thighs of non-injured athletes. The present results suggest that BFLH proximal aponeurosis size should not be considered as an independent risk factor for strain injury.

Neuromuscular control during gait in people with haemophilic arthropathy.

INTRODUCTION: Effects of haemophilic arthropathy on neuromuscular control during gait are currently unknown. AIMS: (a) To assess how haemophilic arthropathy affects the complexity of neuromuscular control during gait; (b) To investigate the relationship between complexity of neuromuscular control and joint impairment. METHODS: Thirteen control subjects (CG) walked overground at their preferred and a slow velocity and thirteen people with haemophilic arthropathy (PWHA) walking at their preferred velocity. Surface electromyography (EMG) was collected from eleven leg muscles. Electromyography variance explained by muscle synergies (sets of co-activated muscles that can be recruited by a single signal) was calculated by the total variance accounted (tVAF). Three measures were used to evaluate complexity of neuromuscular control: (a) the number of synergies required for tVAF > 90%, (b) tVAF as a function of the number of muscle synergies, and (c) the dynamic motor control index (Walk-DMC). Impairment of ankle and knee joints was determined by the Haemophilia Joint Health Score (HJHS). RESULTS: The same number of the muscle synergies was found for each group (P > 0.05). For both walking velocities tested, tVAF1 was higher in PHWA (P < 0.05). The Walk-DMC of PWHA was lower than that of the CG for both walking velocities (P < 0.05). For PWHA, no significant correlation was found between HJHS (sum knee and ankle) and Walk-DMC index (r = -0.32, P = 0.28). CONCLUSIONS: These results indicate differences between PWHA and CG in the neuromuscular control of gait. The Walk-DMC and tVAF1 may be useful measures to assess changes in neuromuscular control in response to treatment.

In vivo relationship between pelvis motion and deep fascia displacement of the medial gastrocnemius: anatomical and functional implications.

Different authors have modelled myofascial tissue connectivity over a distance using cadaveric models, but in vivo models are scarce. The aim of this study was to evaluate the relationship between pelvic motion and deep fascia displacement in the medial gastrocnemius (MG). Deep fascia displacement of the MG was evaluated through automatic tracking with an ultrasound. Angular variation of the pelvis was determined by 2D kinematic analysis. The average maximum fascia displacement and pelvic motion were 1.501 ±â€…0.78 mm and 6.55 ±â€…2.47 °, respectively. The result of a simple linear regression between fascia displacement and pelvic motion for three task executions by 17 individuals was r = 0.791 (P < 0.001). Moreover, hamstring flexibility was related to a lower anterior tilt of the pelvis (r = 0.544, P < 0.024) and a lower deep fascia displacement of the MG (r = 0.449, P < 0.042). These results support the concept of myofascial tissue connectivity over a distance in an in vivo model, reinforce the functional concept of force transmission through synergistic muscle groups, and grant new perspectives for the role of fasciae in restricting movement in remote zones.

Bleomycin-induced γH2AX foci map preferentially to replicating domains in CHO9 interphase nuclei.

Exposure to DNA damaging agents triggers phosphorylation of histone variant H2AX (generating γH2AX) in large chromatin regions flanking DNA lesions, allowing their immunodetection as nuclear foci. Even though a predominance of γH2AX foci in euchromatin has been postulated, foci positioning when DNA insult occurs in replicating eu- or heterochromatin regions has not been extensively explored. Labeling of interphase nuclei with 5-ethynyl-2'-deoxyuridine (EdU) pulses has revealed that DNA replication is temporarily and spatially regulated: euchromatin replicates in early S (ES) and heterochromatin along mid and late S (MS/LS) phases. In order to map DNA damage with respect to replicating domains, the distribution of γH2AX foci induced by the radiomimetic agent bleomycin was analyzed in CHO9 interphase nuclei by delineating euchromatic (H3K4me3+) and replicating (EdU+) regions. Quantification of overlapping pixels and 3D inter-object overlap in binary masks revealed colocalization between γH2AX foci and EdU + domains both in ES and MS/LS nuclei, indicating that primary damage distribution is modulated by DNA synthesis. Further, we verified that EdU incorporation by itself did not influence BLEO-induced γH2AX nuclear patterns. Our results also revealed a repeated localization of γH2AX foci in replicating/nonreplicating interfaces which could reflect short-range chromatin migration following DNA insult.

Cochlear dysfunction as an early biomarker of cognitive decline in normal hearing and mild hearing loss.

INTRODUCTION: Age-related hearing loss is an important risk factor for cognitive decline. However, audiogram thresholds are not good estimators of dementia risk in subjects with normal hearing or mild hearing loss. Here we propose to use distortion product otoacoustic emissions (DPOAEs) as an objective and sensitive tool to estimate the risk of cognitive decline in older adults with normal hearing or mild hearing loss. METHODS: We assessed neuropsychological, brain magnetic resonance imaging, and auditory analyses on 94 subjects > 64 years of age. RESULTS: We found that cochlear dysfunction, measured by DPOAEs-and not by conventional audiometry-was associated with Clinical Dementia Rating Sum of Boxes (CDR-SoB) classification and brain atrophy in the group with mild hearing loss (25 to 40 dB) and normal hearing (<25 dB). DISCUSSION: Our findings suggest that DPOAEs may be a non-invasive tool for detecting neurodegeneration and cognitive decline in the older adults, potentially allowing for early intervention.

Psychological factors are associated with pain extent in patients with carpal tunnel syndrome.

INTRODUCTION: Widespread pain may be related to psychosocial aspects in several musculoskeletal conditions, but the literature on carpal tunnel syndrome (CTS) is scarce. OBJECTIVE: To determine the relationship between pain extent and psychological factors (catastrophizing, kinesiophobia, anxiety symptoms, and depression) in people with CTS. METHODS: A cross-sectional study was conducted. The independent variables were: pain intensity, disability (QuickDASH), duration of symptoms, anxiety and depressive symptoms, catastrophizing, and kinesiophobia. The main outcome was: pain extent (% of total area and categories "pain within the median nerve-innervated territory" versus "extra-median nerve pain"). Correlation analysis was performed using Spearman's correlation coefficient. A linear regression model and binary logistic regression (both with forward selection) were performed to determine the main predictors of pain extent. RESULTS: Forty-eight participants were included. A moderate positive correlation was found between catastrophizing (r = 0.455; p = 0.024) and disability (r = 0.448; p = 0.024) with total pain extent area. Regression models indicated that catastrophizing explained 22% of the variance in the pain extent (ß = 0.003; 95% CI: 0.002-0.005), while kinesiophobia was the variable that best explained the distribution of pain in the extra-median territory (R2 Nagelkerke = 0.182). Null or weak correlations were found for the rest of the associations. CONCLUSION: Catastrophizing and kinesiophobia were the main indicators of pain extent in people with CTS. Clinicians are advised to use specific questionnaires to check for the presence of catastrophizing or kinesiophobia in people with CTS and wider pain extension.

Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Asymmetry in neural fields: a spatiotemporal encoding mechanism.

Neural field models have been successfully applied to model diverse brain mechanisms like visual attention, motor control, and memory. Most theoretical and modeling works have focused on the study of the dynamics of such systems under variations in neural connectivity, mainly symmetric connectivity among neurons. However, less attention has been given to the emerging properties of neuron populations when neural connectivity is asymmetric, although asymmetric activity propagation has been observed in cortical tissue. Here we explore the dynamics of neural fields with asymmetric connectivity and show, in the case of front propagation, that it can bias the population to follow a certain trajectory with higher activation. We find that asymmetry relates linearly to the input speed when the input is spatially localized, and this relation holds for different kernels and input shapes. To illustrate the behavior of asymmetric connectivity, we present an application: standard video sequences of human motion were encoded using the asymmetric neural field and compared to computer vision techniques. Overall, our results indicate that asymmetric neural fields are a competitive approach for spatiotemporal encoding with two main advantages: online classification and distributed operation.

Detection of intermuscular coordination based on the causality of empirical mode decomposition.

Considering the stochastic nature of electromyographic (EMG) signals, nonlinear methods may be a more accurate approach to study intermuscular coordination than the linear approach. The aims of this study were to assess the coordination between two ankle plantar flexors using EMG by applying the causal decomposition approach and assessing whether the intermuscular coordination is affected by the slope of the treadmill. The medial gastrocnemius (MG) and soleus muscles (SOL) were analyzed during the treadmill walking at inclinations of 0°, 5°, and 10°. The coordination was evaluated using ensemble empirical mode decomposition, and the causal interaction was encoded by the instantaneous phase dependence of time series bi-directional causality. To estimate the mutual predictability between MG and SOL, the cross-approximate entropy (XApEn) was assessed. The maximal causal interaction was observed between 40 and 75 Hz independent of inclination. XApEn showed a significant decrease between 0° and 5° (p = 0.028), between 5° and 10° (p = 0.038), and between 0° and 10° (p = 0.014), indicating an increase in coordination. Thus, causal decomposition is an appropriate methodology to study intermuscular coordination. These results indicate that the variation of loading through the change in treadmill inclination increases the interaction of the shared input between MG and SOL, suggesting increased intermuscular coordination.

Assessing subjective cognitive decline in older adults attending primary health care centers: what question should be asked?

INTRODUCTION: Subjective Cognitive Decline (SCD) refers to a self-perceived experience of decreased cognitive function without objective signs of cognitive impairment in neuropsychological tests or daily living activities. Despite the abundance of instruments addressing SCD, there is no consensus on the methods to be used. Our study is founded on 11 questions selected due to their recurrence in most instruments. The objective was to determine which one of these questions could be used as a simple screening tool. METHODS: 189 participants aged 65 and over selected from Primary Care centers in Santiago de Chile responded to these 11 questions and were evaluated with the MiniMental State Examination (MMSE), the Free and Cued Selective Reminding Test (FCSRT), the Pfeffer functional scale, and the Geriatric Depression Scale (GDS). An Item ResponseTheory (IRT) method was performed to assess the contribution of each of the 11 questions to the SCD latent trait and its discrimination ability. RESULTS: Based on the results of the exploratory factor analysis showing very high/low saturation of several questions on the factors, and the high residual correlation between some questions, the IRT methods led to select one question ("Do you feel like your memory has become worse?") which revealed to be the most contributive and discriminant. Participants who answered yes had a higher GDS score. There was no association with MMSE, FCSRT, and Pfeffer scores. CONCLUSION: The question "Do you feel like your memory has become worse?" may be a good proxy of SCD and could be included in routine medical checkups.

The "when" matters: Evidence from memory markers in the clinical continuum of Alzheimer's disease.

OBJECTIVE: Cognitive assessment able to detect impairments in the early neuropathological stages of Alzheimer's disease (AD) is urgently needed. The visual short-term memory binding task (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) have been recommended by the neurodegenerative disease working group as promising tests to aid in the early detection of AD. In this study, we investigated their complementary value across the clinical stages of the AD continuum. METHOD: One hundred and seventeen older adults with subjective cognitive complaint (SCC), 79 with mild cognitive impairment (MCI), 31 patients with AD dementia (ADD), and 37 cognitively unimpaired (CU) subjects, underwent assessment with the VSTMBT and the picture version of the Spanish FCSRT. RESULTS: After controlling for multiple comparisons, significant differences were found across groups. The VSTMBT was the only test that "marginally" differentiated between CU and SCC (d = 0.47, p = .052). Moreover, whereas the FCSRT showed a gradient (CU = SCC) > MCI > ADD, the VSTMBT gradient was CU > SCC > (MCI = ADD) suggesting that conjunctive binding deficits assessed by the latter may be sensitive to the very early stages of the disease. CONCLUSIONS: Our results suggest that the VSTMBT and the FCSRT are sensitive to the clinical continuum of AD. Whereas the former detects changes in the early prodromal stages, the latter is more sensitive to the advanced prodromal stages of AD. These novel tests can aid in the early detection, monitor disease progression and response to treatment, and thus support drug development programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Protocol for extracting live blastoderm cells from embryos of annual killifish.

The implementation of in vitro approaches using undifferentiated embryonic cells from annual killifish to complement existing in vivo developmental studies has been hindered by a lack of efficient isolation techniques. Here, we present a protocol to isolate annual killifish blastoderm cells, at the epiboly and early dispersion phase, from embryos. We describe steps for hair removal, embryo cleaning, dechorionation, and cell purification. This protocol may also be used to develop strategies to isolate cells from embryos presenting similar challenges.

The limitations and challenges in the assessment of executive dysfunction associated with real-world functioning: The opportunity of serious games.

Nowadays, there is a broad range of methods for detecting and evaluating executive dysfunction ranging from clinical interview to neuropsychological evaluation. Nevertheless, a critical issue of these assessments is the lack of correspondence of the neuropsychological test's results with real-world functioning. This paper proposes serious games as a new framework to improve the neuropsychological assessment of real-world functioning. We briefly discuss the contribution and limitations of current methods of evaluation of executive dysfunction (paper-and-pencil tests, naturalistic observation methods, and Information and Communications Technologies) to inform on daily life functioning. Then, we analyze what are the limitations of these methods to predict real-world performance: (1) A lack of appropriate instruments to investigate the complexity of real-world functioning, (2) the vast majority of neuropsychological tests assess well-structured tasks, and (3) measurement of behaviors are based on simplistic data collection and statistical analysis. This work shows how serious games offer an opportunity to develop more efficient tools to detect executive dysfunction in everyday life contexts. Serious games provide meaningful narrative stories and virtual or real environments that immerse the user in natural and social environments with social interactions. In those highly interactive game environments, the player needs to adapt his/her behavioral performance to novel and ill-structured tasks which are suited for collecting user interaction evidence. Serious games offer a novel opportunity to develop better tools to improve diagnosis of the executive dysfunction in everyday life contexts. However, more research is still needed to implement serious games in everyday clinical practice.