Repetitive active and passive cognitive stimulations induce EEG changes in patients with Rett syndrome.

BACKGROUND: Despite being considered a rare disease, Rett syndrome is a leading cause of profound cognitive impairment in females. This study explores game-based cognitive stimulation to enhance attention during learning tasks, offering an alternative treatment perspective. METHODS: Fifteen diagnosed Rett syndrome girls participated in four 24-minute sessions, including a 5-minute initial resting state recording. Primary indicators for analysis included relative power and spectral entropy. RESULTS: Significant findings indicated variations among conditions (resting state, active task, passive task) in response to stimulation. Notably, over four days, evolution occurred, characterized by decreasing delta power and increasing theta and beta power. Topographic maps confirmed these shifts, highlighting affected brain areas. Linear regression emphasized the most significant impact on the first day, with subsequent shifts towards higher frequencies, particularly during the resting state. By the fourth day, resting-state patterns resembled those during cognitive activities. CONCLUSION: Findings suggest cognitive stimulation induces substantial EEG spectral changes, potentially linked to cognitive enhancements in Rett syndrome. The shift towards higher frequency bands and increased spectral entropy align with enhanced brain activation during cognitive sessions, underscoring the potential of cognitive stimulation therapies and calling for further research to optimize abilities in individuals with Rett syndrome. IMPACT: Game-based cognitive stimulation induces substantial EEG changes in individuals with Rett syndrome, enhancing cognitive functions, notably attention during learning. This study conducts a distinctive examination, assessing the habituation paradigm through the combination of game-based cognitive stimulation and learning, providing valuable insights into enhancing attention in Rett syndrome. Impacting understanding of cognitive processes in Rett syndrome, this research reveals significant EEG variations during tasks, emphasizing the potential of cognitive stimulation for attention enhancement and the need for further research in tailored interventions.

Individualized time windows enhance TMS-EEG signal characterization and improve assessment of cortical function in schizophrenia.

Transcranial magnetic stimulation and electroencephalography (TMS-EEG) recordings are crucial to directly assess cortical excitability and inhibition in a non-invasive and task-free manner. TMS-EEG signals are characterized by TMS-evoked potentials (TEPs), which are employed to evaluate cortical function. Nonetheless, different time windows (TW) have been used to compute them over the years. Moreover, these TWs tend to be the same for all participants omitting the intersubject variability. Therefore, the objective of this study is to assess the effect of using different TWs to compute the TEPs, moving from a common fixed TW to more adaptive individualized TWs. Twenty-nine healthy (HC) controls and twenty schizophrenia patients (SCZ) underwent single-pulse (SP) TMS-EEG protocol. Firstly, only the HC were considered to evaluate the TEPs for three different TWs in terms of amplitude and topographical distribution. Secondly, the SCZ patients were included to determine which TW is better to characterize the brain alterations of SCZ. The results indicate that a more individualized TW provides a better characterization of the SP TMS-EEG signals, although all of them show the same tendency. Regarding the comparison between groups, the individualized TW is the one that provides a better differentiation between populations. They also provide further support to the possible imbalance of cortical excitability/inhibition in the SCZ population due to its reduced activity in the N45 TEP and greater amplitude values in the N100. Results also suggest that the SCZ brain has a baseline hyperactive state since the TEPs of the SCZ appear earlier than those of the HC.

Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS-EEG study.

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity-as an index of the inhibitory function-was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.

Methodological biases in observational hospital studies of COVID-19 treatment effectiveness: pitfalls and potential.

Introduction: This study aims to discuss and assess the impact of three prevalent methodological biases: competing risks, immortal-time bias, and confounding bias in real-world observational studies evaluating treatment effectiveness. We use a demonstrative observational data example of COVID-19 patients to assess the impact of these biases and propose potential solutions. Methods: We describe competing risks, immortal-time bias, and time-fixed confounding bias by evaluating treatment effectiveness in hospitalized patients with COVID-19. For our demonstrative analysis, we use observational data from the registry of patients with COVID-19 who were admitted to the Bellvitge University Hospital in Spain from March 2020 to February 2021 and met our predefined inclusion criteria. We compare estimates of a single-dose, time-dependent treatment with the standard of care. We analyze the treatment effectiveness using common statistical approaches, either by ignoring or only partially accounting for the methodological biases. To address these challenges, we emulate a target trial through the clone-censor-weight approach. Results: Overlooking competing risk bias and employing the naïve Kaplan-Meier estimator led to increased in-hospital death probabilities in patients with COVID-19. Specifically, in the treatment effectiveness analysis, the Kaplan-Meier estimator resulted in an in-hospital mortality of 45.6% for treated patients and 59.0% for untreated patients. In contrast, employing an emulated trial framework with the weighted Aalen-Johansen estimator, we observed that in-hospital death probabilities were reduced to 27.9% in the "X"-treated arm and 40.1% in the non-"X"-treated arm. Immortal-time bias led to an underestimated hazard ratio of treatment. Conclusion: Overlooking competing risks, immortal-time bias, and confounding bias leads to shifted estimates of treatment effects. Applying the naïve Kaplan-Meier method resulted in the most biased results and overestimated probabilities for the primary outcome in analyses of hospital data from COVID-19 patients. This overestimation could mislead clinical decision-making. Both immortal-time bias and confounding bias must be addressed in assessments of treatment effectiveness. The trial emulation framework offers a potential solution to address all three methodological biases.

EEG connectivity patterns in response to gaming and learning-based cognitive stimulations in Rett syndrome.

BACKGROUND: Functional connectivity is scarcely studied in Rett syndrome (RTT). Explorations revealed associations between RTT's clinical, genetic profiles, and coherence measures, highlighting an unexplored frontier in understanding RTT's neural mechanisms and cognitive processes. AIMS: To evaluate the effects of diverse cognitive stimulations-learning-focused versus gaming-oriented-on electroencephalography brain connectivity in RTT. The comparison with resting states aimed to uncover potential biomarkers and insights into the neural processes associated with RTT. METHODS AND PROCEDURES: The study included 15 girls diagnosed with RTT. Throughout sessions lasting about 25 min, participants alternated between active and passive tasks, using an eyetracker device while their brain activity was recorded with a 20-channel EEG. Results revealed significant alterations during cognitive tasks, notably in delta, alpha and beta bands. Both tasks induced spectral pattern changes and connectivity shifts, hinting at enhanced neural processing. Hemispheric asymmetry decreased during tasks, suggesting more balanced neural processing. Linear and nonlinear connectivity alterations were observed in active tasks compared to resting state, while passive tasks showed no significant changes. CONCLUSIONS AND IMPLICATIONS: Results underscores the potential of cognitive stimulation for heightened cognitive abilities, promoting enhanced brain connectivity and information flow in Rett syndrome. These findings offer valuable markers for evaluating cognitive interventions and suggest gaming-related activities as effective tools for improving learning outcomes.