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Abstract Comprehending digital content written in natural language online is vital for many aspects of life, including learning, professional tasks, and decision-making. However, facing comprehension difficulties can have negative consequences for learning outcomes, critical thinking skills, decision-making, error rate, and productivity. This paper introduces an innovative approach to predict comprehension difficulties at the local content level (e.g., paragraphs). Using affordable wearable devices, we acquire physiological responses non-intrusively from the autonomous nervous system, specifically pulse rate variability, and electrodermal activity. Additionally, we integrate data from a cost-effective eye-tracker. Our machine learning algorithms identify ’hotspots’ within the content and regions corresponding to a high cognitive load. These hotspots represent real-time predictors of comprehension difficulties. By integrating physiological data with contextual information (such as the levels of experience of individuals), our approach achieves an accuracy of 72.11% ± 2.21, a precision of 0.77, a recall of 0.70, and an f1 score of 0.73. This study opens possibilities for developing intelligent, cognitive-aware interfaces. Such interfaces can provide immediate contextual support, mitigating comprehension challenges within content. Whether through translation, content generation, or content summarization using available Large Language Models, this approach has the potential to enhance language comprehension.

Cognitive human error and recent cognitive taxonomy on human error causes of software defects support the intuitive idea that, for instance, mental overload, attention slips, and working memory overload are important human causes for software bugs. In this paper, we approach the EEG as a reliable surrogate to MRI-based reference of the programmer's cognitive state to be used in situations where heavy imaging techniques are infeasible. The idea is to use EEG biomarkers to validate other less intrusive physiological measures, that can be easily recorded by wearable devices and useful in the assessment of the developer's cognitive state during software development tasks. Herein, our EEG study, with the support of fMRI, presents an extensive and systematic analysis by inspecting metrics and extracting relevant information about the most robust features, best EEG channels and the best hemodynamic time delay in the context of software development tasks. From the EEG-fMRI similarity analysis performed, we found significant correlations between a subset of EEG features and the Insula region of the brain, which has been reported as a region highly related to high cognitive tasks, such as software development tasks. We concluded that despite a clear inter-subject variability of the best EEG features and hemodynamic time delay used, the most robust and predominant EEG features, across all the subjects, are related to the Hjorth parameter Activity and Total Power features, from the EEG channels F4, FC4 and C4, and considering in most of the cases a hemodynamic time delay of 4 seconds used on the hemodynamic response function. These findings should be taken into account in future EEG-fMRI studies in the context of software debugging.

Abstract Invasive brain recordings using many electrodes across a wide range of tasks provide a unique opportunity to study the role of oscillatory patterning and functional connectivity. We used large-scale recordings (stereo EEG) within and beyond the human hippocampus to investigate the role of distinct frequency oscillations during real-time execution of visual, attention and memory tasks in eight epileptic patients. We found that activity patterns in the hippocampus showed task and frequency dependent properties. Importantly, we found distinct connectivity signatures, in particular concerning parietal-hippocampal connectivity, thus revealing large scale synchronization of networks involved in memory tasks. Comparing the power per frequency band, across tasks and hippocampal regions (anterior/posterior) we confirmed a main effect of frequency band (p = 0.002). Gamma band activity was higher for visuo-spatial memory tasks in the anterior hippocampus. Further, we found that alpha and beta band activity in posterior hippocampus had larger modulation for high memory load visual tasks (p = 0.004). Three functional connectivity task related networks were identified: (dorsal) parietal-hippocampus (visual attention and memory), ventral stream- hippocampus and hippocampal-frontal connections (mainly tasks involving face recognition or object based search). These findings support the critical role of oscillatory patterning in the hippocampus during visual and memory tasks and suggests the presence of task related spectral and functional connectivity signatures. These results show that the use of large scale human intracranial recordings can validate the role of oscillatory and functional connectivity patterns across a broad range of cognitive domains.

Abstract Machado-Joseph disease (MJD) or Spinocerebellar ataxia type 3 (SCA3) is the most common form of dominant SCA worldwide. Magnetic Resonance Imaging (MRI) and Proton Magnetic Resonance Spectroscopy (1H-MRS) provide promising non-invasive diagnostic and follow-up tools, also serving to evaluate therapies efficacy. However, pre-clinical studies showing relationship between MRI-MRS based biomarkers and functional performance are missing, which hampers an efficient clinical translation of therapeutics. This study assessed motor behaviour, neurochemical profiles, and morphometry of the cerebellum of MJD transgenic mice and patients aiming at establishing magnetic-resonance-based biomarkers. 1H-MRS and structural MRI measurements of MJD transgenic mice were performed with a 9.4 Tesla scanner, correlated with motor performance on rotarod and compared with data collected from human patients. We found decreased cerebellar white and grey matter and enlargement of the fourth ventricle in both MJD mice and human patients as compared to controls. N-acetylaspartate (NAA), NAA + N-acetylaspartylglutamate (NAA + NAAG), Glutamate, and Taurine, were significantly decreased in MJD mouse cerebellum regardless of age, whereas myo-Inositol (Ins) was increased at early time-points. Lower neurochemical ratios levels (NAA/Ins and NAA/total Choline), previously correlated with worse clinical status in SCAs, were also observed in MJD mice cerebella. NAA, NAA + NAAG, Glutamate, and Taurine were also positively correlated with MJD mice motor performance. Importantly, these 1H-MRS results were largely analogous to those found for MJD in human studies and in our pilot data in human patients. We have established a magnetic resonance-based biomarker approach to monitor novel therapies in preclinical studies and human clinical trials.

Complexity is the key element of software quality. This article investigates the problem of measuring code complexity and discusses the results of a controlled experiment to compare different views and methods to measure code complexity. Participants (27 programmers) were asked to read and (try to) understand a set of programs, while the complexity of such programs is assessed through different methods and perspectives: (a) classic code complexity metrics such as McCabe and Halstead metrics, (b) cognitive complexity metrics based on scored code constructs, (c) cognitive complexity metrics from state-of-the-art tools such as SonarQube, (d) human-centered metrics relying on the direct assessment of programmers’ behavioral features (e.g., reading time, and revisits) using eye tracking, and (e) cognitive load/mental effort assessed using electroencephalography (EEG). The human-centered perspective was complemented by the subjective evaluation of participants on the mental effort required to understand the programs using the NASA Task Load Index (TLX). Additionally, the evaluation of the code complexity is measured at both the program level and, whenever possible, at the very low level of code constructs/code regions, to identify the actual code elements and the code context that may trigger a complexity surge in the programmers’ perception of code comprehension difficulty. The programmers’ cognitive load measured using EEG was used as a reference to evaluate how the different metrics can express the (human) difficulty in comprehending the code. Extensive experimental results show that popular metrics such as V(g) and the complexity metric from SonarSource tools deviate considerably from the programmers’ perception of code complexity and often do not show the expected monotonic behavior. The article summarizes the findings in a set of guidelines to improve existing code complexity metrics, particularly state-of-the-art metrics such as cognitive complexity from SonarSource tools.

Deficits in mitochondrial function and redox deregulation have been attributed to Huntington's disease (HD), a genetic neurodegenerative disorder largely affecting the striatum. However, whether these changes occur in early stages of the disease and can be detected in vivo is still unclear. In the present study, we analysed changes in mitochondrial function and production of reactive oxygen species (ROS) at early stages and with disease progression. Studies were performed in vivo in human brain by PET using [64Cu]-ATSM and ex vivo in human skin fibroblasts of premanifest and prodromal (Pre-M) and manifest HD carriers. In vivo brain [64Cu]-ATSM PET in YAC128 transgenic mouse and striatal and cortical isolated mitochondria were assessed at presymptomatic (3 month-old, mo) and symptomatic (6–12 mo) stages. Pre-M HD carriers exhibited enhanced whole-brain (with exception of caudate) [64Cu]-ATSM labelling, correlating with CAG repeat number. Fibroblasts from Pre-M showed enhanced basal and maximal respiration, proton leak and increased hydrogen peroxide (H2O2) levels, later progressing in manifest HD. Mitochondria from fibroblasts of Pre-M HD carriers also showed reduced circularity, while higher number of mitochondrial DNA copies correlated with maximal respiratory capacity. In vivo animal PET analysis showed increased accumulation of [64Cu]-ATSM in YAC128 mouse striatum. YAC128 mouse (at 3 months) striatal isolated mitochondria exhibited a rise in basal and maximal mitochondrial respiration and in ATP production, and increased complex II and III activities. YAC128 mouse striatal mitochondria also showed enhanced mitochondrial H2O2 levels and circularity, revealed by brain ultrastructure analysis, and defects in Ca2+ handling, supporting increased striatal susceptibility. Data demonstrate both human and mouse mitochondrial overactivity and altered morphology at early HD stages, facilitating redox unbalance, the latter progressing with manifest disease.

ObjectivesWe aimed to investigate the antiepileptic effects of cathodal transcranial direct current stimulation (c-tDCS) and mechanisms of action based on its effects on the neurotransmitters responsible for the abnormal synchrony patterns seen in pharmacoresistant epilepsy. This is the first study to test the impact of neurostimulation on epileptiform interictal discharges (IEDs) and to measure brain metabolites in the epileptogenic zone (EZ) and control regions simultaneously in patients with pharmacoresistant epilepsy.MethodsThis is a hypothesis-driven pilot prospective single-blinded repeated measure design study in patients diagnosed with pharmacoresistant epilepsy of temporal lobe onset. We included seven patients who underwent two sessions of c-tDCS (sham followed by real). The real tDCS session was 20 min in duration and had a current intensity of 1.5 mA delivered via two surface electrodes that had dimensions of 3 × 4 cm. The cathode electrode was placed at FT7 in the center whereas the anode at Oz in the center. After each session, we performed electroencephalographic recording to count epileptiform IEDs over 30 min. We also performed magnetic resonance spectroscopy (MRS) to measure brain metabolite concentrations in the two areas of interest (EZ and occipital region), namely, gamma-aminobutyric acid (GABA), glutamate (Glx), and glutathione. We focused on a homogenous sample where the EZ and antiepileptic medications are shared among patients.ResultsReal tDCS decreased the number of epileptiform IEDs per min (from 9.46 ± 2.68 after sham tDCS to 5.37 ± 3.38 after real tDCS), p = 0.018, as compared to sham tDCS. GABA was decreased in the EZ after real c-tDCS stimulation as compared to sham tDCS (from 0.129 ± 0.019 to 0.096 ± 0.018, p = 0.02). The reduction in EZ GABA correlated with the reduction in the frequency of epileptiform IED per min (rho: 0.9, p = 0.003).ConclusionThese results provide a window into the antiepileptic mechanisms of action of tDCS, based on local and remote changes in GABA and neural oscillatory patterning responsible for the generation of interictal epileptiform discharges.

Error-related electroencephalographic (EEG) signals have been widely studied concerning the human cognitive capability of differentiating between erroneous and correct actions. Midfrontal error-related negativity (ERN) and theta band oscillations are believed to underlie post-action error monitoring. However, it remains elusive how early monitoring activity is trackable and what are the pre-response brain mechanisms related to performance monitoring. Moreover, it is still unclear how task-specific parameters, such as cognitive demand or motor control, influence these processes. Here, we aimed to test pre- and post-error EEG patterns for different types of motor responses and investigate the neuronal mechanisms leading to erroneous actions. We implemented a go/no-go paradigm based on keypresses and saccades. Participants received an initial instruction about the direction of response to be given based on a facial cue and a subsequent one about the type of action to be performed based on an object cue. The paradigm was tested in 20 healthy volunteers combining EEG and eye tracking. We found significant differences in reaction time, number, and type of errors between the two actions. Saccadic responses reflected a higher number of premature responses and errors compared to the keypress ones. Nevertheless, both led to similar EEG patterns, supporting previous evidence for increased ERN amplitude and midfrontal theta power during error commission. Moreover, we found pre-error decreased theta activity independent of the type of action. Source analysis suggested different origin for such pre- and post-error neuronal patterns, matching the anterior insular cortex and the anterior cingulate cortex, respectively. This opposite pattern supports previous evidence of midfrontal theta not only as a neuronal marker of error commission but also as a predictor of action performance. Midfrontal theta, mostly associated with alert mechanisms triggering behavioral adjustments, also seems to reflect pre-response attentional mechanisms independently of the action to be performed. Our findings also add to the discussion regarding how salience network nodes interact during performance monitoring by suggesting that pre- and post-error patterns have different neuronal sources within this network.

Error monitoring is the metacognitive process by which we are able to detect and signal our errors once a response has been made. Monitoring when the outcome of our actions deviates from the intended goal is crucial for behavior, learning, and the development of higher-order social skills. Here, we explored the neuronal substrates of error monitoring during the integration of facial expression cues using electroencephalography (EEG). Our goal was to investigate the signatures of error monitoring before and after a response execution dependent on the integration of facial cues. We followed the hypothesis of midfrontal theta as a robust neuronal marker of error monitoring since it has been consistently described as a mechanism to signal the need for cognitive control. Also, we hypothesized that EEG frequency-domain components might bring advantage to study error monitoring in complex scenarios as it carries information from locked and non-phase-locked signals. A challenging go/no-go saccadic paradigm was applied to elicit errors: integration of facial emotional signals and gaze direction was required to solve it. EEG data were acquired from twenty healthy participants and analyzed at the level of theta band activity during response preparation and execution. Although theta modulation has been consistently demonstrated during error monitoring, it is still unclear how early it starts to occur. We found theta power differences at midfrontal channels between correct and error trials. Theta was higher immediately after erroneous responses. Moreover, before response initiation we observed the opposite: lower theta preceding errors. These results suggest theta band activity not only as an index of error monitoring, which is needed to enhance cognitive control, but also as a requisite for success. This study adds to previous evidence for the role of theta band in error monitoring processes by revealing error-related patterns even before response execution in complex tasks, and using a paradigm requiring the integration of facial expression cues.

Introduction. To design more effective interventions, such as neurostimulation, for stroke rehabilitation, there is a need to understand early physiological changes that take place that may be relevant for clinical monitoring. We aimed to study changes in neurophysiology following recent ischemic stroke, both at rest and with motor planning and execution. Materials and Methods. We included 10 poststroke patients, between 7 and 10 days after stroke, and 20 age-matched controls to assess changes in cortical motor output via transcranial magnetic stimulation and in dynamics of oscillations, as recorded using electroencephalography (EEG). Results. We found significant differences in cortical oscillatory patterns comparing stroke patients with healthy participants, particularly in the beta rhythm during motor planning (p=0.011) and execution (p=0.004) of a complex movement with fingers from both hands simultaneously. Discussion. The stroke lesion induced a decrease in event-related desynchronization in patients, in comparison to controls, providing evidence for decreased disinhibition. Conclusions. After a stroke lesion, the dynamics of cortical oscillations is changed, with an increasing neural beta synchronization in the course of motor preparation and performance of complex bimanual finger tasks. The observed patterns may provide a potential functional measure that could be used to monitor and design interventional approaches in subacute stages.

Background: Several functional magnetic resonance imaging (fMRI) studies investigated the brain correlates of psychogenic erectile dysfunction (PED) and premature ejaculation (PE), representing the most common sexual dysfunctions in men. These studies allowed a wide set of brain regions in PED and PE patients when compared to healthy men. In the present meta-analysis, we aim at assessing the presence of homogeneity in the cerebral underpinnings of PED and PE. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and after the electronic search, duplicate removal and the application of pre-exclusion criteria, nine PED and ten PE studies were considered eligible with a Cohen’s k of 0.84 and 0.75, respectively. The effect sizes of the sociodemographic and psychological/urological dimensions were calculated. We extracted brain clusters from the retrieved studies, comparing patients and controls, and we calculated brain maps with Seed-Based D Mapping software. Results: We found a homogenous involvement of the frontal gyrus and insula in both dysfunctions, suggesting a common network. Conclusions: The anterior insula plays a key role in the processing of emotional features of stimuli, while the posterior insula in interoceptive information is relevant for sexual response. The prefrontal and inferior frontal cortices are important for sexual inhibition/disinhibition.

Being social animals, rats exhibit a range of social behaviors that help them build social bonds and maintain group cohesion. Behavior is influenced by multiple factors, including stress exposure, and the expression of the impact of stress on both social and non-social behaviors may also be aected by the living conditions of rats. In this study, we explored the physiological and behavioral eects of chronic unpredictable stress on group-housed rats in the PhenoWorld (PhW), a socially and physically enriched environment closer to real-life conditions. Two independent experiments were performed: one in the control condition (PhW control, n = 8) and one in the stress condition (PhW stress, n = 8). Control animals remained undisturbed except for cage cleaning and daily handling procedures. Stress group animals were all exposed to chronic unpredictable stress. Data confirm that stress exposure triggers anxiety-like behavior in the PhW. In terms of home-cage behaviors, we found that stress aects social behaviors (by decreased playing and increased huddling behaviors) and non-social behaviors (as shown by the decrease in rearing and walking behaviors). These results are of relevance to expand our knowledge on the influence of stress on social and non-social behaviors, which are of importance to understand better species-typical behaviors. [ABSTRACT FROM AUTHOR]

The neural correlates of software programming skills have been the target of an increasing number of studies in the past few years. Those studies focused on error-monitoring during software code inspection. Others have studied task-related cognitive load as measured by distinct neurophysiological measures. Most studies addressed only syntax errors (shallow level of code monitoring). However, a recent functional MRI (fMRI) study suggested a pivotal role of the insula during error-monitoring when challenging deep-level analysis of code inspection was required. This raised the hypothesis that the insula is causally involved in deep error-monitoring. To confirm this hypothesis, we carried out a new fMRI study where participants performed a deep source-code comprehension task that included error-monitoring to detect bugs in the code. The generality of our paradigm was enhanced by comparison with a variety of tasks related to text reading and bugless source-code understanding. Healthy adult programmers (N = 21) participated in this 3T fMRI experiment. The activation maps evoked by error-related events confirmed significant activations in the insula [p(Bonferroni) < 0.05]. Importantly, a posterior-to-anterior causality shift was observed concerning the role of the insula: in the absence of error, causal directions were mainly bottom-up, whereas, in their presence, the strong causal top-down effects from frontal regions, in particular, the anterior cingulate cortex was observed.

Being social animals, rats exhibit a range of social behaviors that help them build social bonds and maintain group cohesion. Behavior is influenced by multiple factors, including stress exposure, and the expression of the impact of stress on both social and non-social behaviors may also be affected by the living conditions of rats. In this study, we explored the physiological and behavioral effects of chronic unpredictable stress on group-housed rats in the PhenoWorld (PhW), a socially and physically enriched environment closer to real-life conditions. Two independent experiments were performed: one in the control condition (PhW control, n = 8) and one in the stress condition (PhW stress, n = 8). Control animals remained undisturbed except for cage cleaning and daily handling procedures. Stress group animals were all exposed to chronic unpredictable stress. Data confirm that stress exposure triggers anxiety-like behavior in the PhW. In terms of home-cage behaviors, we found that stress affects social behaviors (by decreased playing and increased huddling behaviors) and non-social behaviors (as shown by the decrease in rearing and walking behaviors). These results are of relevance to expand our knowledge on the influence of stress on social and non-social behaviors, which are of importance to understand better species-typical behaviors.