Examining the Effects of Bright Light Therapy on Sleep and Resting-State Brain Activity in Parkinson’s Disease: A Randomized Crossover Pilot Study

Han-Xing Li,1,* Ming-Hui Tang,1,* Qin-Jie Zhou,1 Jin Dai,2 Wei-Ye Xie,1 Meng-Xing Tao,1 Chun-Feng Liu,1,3,4 Yun Shen1,51Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China; 2The People’s Hospital of Songtao Miao Autonomous County, Tongren, 554100, People’s Republic of China; 3Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, Suzhou, 215123, People’s Republic of China; 4Department of Neurology, Xiongan Xuanwu Hospital, Xiongan, 071700, People’s Republic of China; 5State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, 210000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun-Feng Liu, Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Gusu District, Suzhou, People’s Republic of China, Email [email protected] Yun Shen, Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Gusu District, Suzhou, People’s Republic of China, Email [email protected]: Sleep disturbances are highly prevalent in patients with Parkinson’s disease (PD). Bright light therapy (BLT) seems to be a promising non-pharmacological intervention for sleep disturbance in PD. However, the neural mechanisms underlying BLT remain unclear. In this pilot study, we aimed to explore the clinical effects of BLT on sleep and to explore potential accompanying changes in brain activity and functional connectivity.Patients and methods: In this randomized, crossover, self-controlled pilot study, BLT was delivered using bright light at 10,000 lux, and dim light at 200 lux served as the control condition. Twenty-seven patients with PD were assigned to receive 30 days of BLT and 30 days of dim light therapy (DLT) in counterbalanced order, separated by a 30-day washout period. Clinical assessments of sleep, polysomnography (PSG) and resting-state functional magnetic resonance imaging (rs-fMRI) were performed at four time points: baseline, following the first intervention phase, following the washout period, and following the second intervention phase.Results: Compared with DLT, BLT was associated with a significantly greater reduction in Epworth Sleepiness Scale (ESS) scores (P=0.012) and tonic REM sleep without atonia (RWA) (P=0.002). In resting-state fMRI, no clusters showed significant alterations in fractional amplitude of low-frequency fluctuation (fALFF) or dynamic fALFF (dfALFF) after BLT compared to DLT. Functional connectivity (FC) analyses using the bilateral thalamus, bilateral calcarine cortex, and bilateral posterior cingulate cortex as seed ROIs revealed no clusters with significant between-intervention connectivity differences after multiple comparison correction.Conclusion: BLT improved excessive daytime sleepiness and reduced tonic RWA relative to control light in PD, but did not lead to detectable alterations in intrinsic activity or FC within a priori hypothesized thalamo-cortical or visual pathways. These findings warrant further validation in larger, long-term studies.Keywords: Parkinson’s disease, sleep, functional magnetic resonance imaging