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. 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. 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. 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. 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.
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