Well-being decline during adolescence: school transition as a predominant driver beyond age progression.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by widespread neuronal loss and gliosis in the central nervous system, particularly affecting striatonigral, olivopontocerebellar, and central autonomic structures. Clinically, MSA presents a diverse spectrum of progressive autonomic, parkinsonian, cerebellar, and pyramidal symptoms. It is classified into two subtypes based on the predominant motor phenotype: parkinsonian (MSA-P) and cerebellar (MSA-C). However, the overlap and variability of these clinical features pose significant challenges for early diagnosis. Current diagnostic approaches rely heavily on clinical observations and patient-reported outcomes, which often lack the sensitivity and specificity needed to monitor disease progression or assess therapeutic efficacy in clinical trials. Consequently, identifying reliable and quantifiable biomarkers for MSA is critical for advancing future research. Oculomotor assessment is an essential part of the neurological examination, as it involves neural circuits spanning the cerebrum, brainstem, and cerebellum. In MSA, typical abnormal oculomotor features include gaze-induced nystagmus, mild to moderate hypometria of saccades, impaired smooth pursuit (SP) eye movements with decreased gain, and excessive square-wave jerks. Among these, saccadic abnormalities are a highly prevalent impairment in patients with MSA and are considered to hold potential as diagnostic biomarkers. The antisaccade (AS) task, which requires suppression of reflexive responses, largely depends on frontostriatal circuits, and their modulation by the superior colliculus and cerebellum. This task has been shown to correlate with disease progression in Parkinson's disease (PD), where nigrostriatal deficits disrupt frontostriatal circuits. Given MSA involves more extensive neurodegeneration in these pathways compared to PD, similar AS impairments may reflect MSA progression. However, these oculomotor impairments have been scarcely studied in MSA. Recent virtual reality (VR)- based quantitative eye movement assessments present several advantages over traditional approaches. First, this approach enables sensitive detection of clinically significant oculomotor signatures with high objectivity and reproducibility, independent of clinician experience required for bedside assessment. Moreover, VR delivers stimuli in an immersive three-dimensional environment that minimizes external interference and elicits natural gaze behaviors, providing a closer approximation to real-world dynamics than the static screens used in traditional quantitative assessments. Additionally, the intuitive interface and portability of VR systems facilitate efficient and accessible operation in diverse settings.