Effects of intermittent theta burst stimulation combined with hyperbaric oxygen therapy on cognitive function and cerebral blood flow in patients with post-stroke mild cognitive impairment

Objective To observe the effects of intermittent theta burst stimulation (iTBS) combined with hyperbaric oxygen therapy on cognitive function and cortical hemodynamics in patients with post-stroke mild cognitive impairment using functional near-infrared spectroscopy (fNIRS). Methods Sixty patients with post-stroke mild cognitive impairment were randomly assigned to an observation group and a control group (30 cases per group). All patients received hyperbaric oxygen therapy and routine cognitive training for 6 weeks, while the observation group additionally received intermittent theta-burst stimulation (iTBS). Before and after the intervention, the Mini-Mental State Examination (MMSE) was used to assess global cognitive function, and functional near-infrared spectroscopy (fNIRS) was used to detect task-evoked cortical oxygenated hemoglobin (Oxy-Hb) responses, including prefrontal Oxy-Hb integral values and channel-wise Oxy-Hb β values representing cortical activation intensity. Paired t -tests were used for within-group comparisons of pre- and post-treatment MMSE scores and prefrontal Oxy-Hb integral values. Analysis of covariance (ANCOVA) with baseline values as covariates was performed for between-group comparisons after treatment. For channel-wise β values, a two-way mixed-design ANOVA was used to test group × time interactions, with group as a between-subject factor and time as a within-subject factor, followed by FDR-corrected simple effects analyses for post hoc comparisons. Results Baseline demographic and clinical characteristics did not differ significantly between the two groups (all p > 0.05). No significant baseline differences were detected in MMSE scores, prefrontal Oxy-Hb integral values, or channel-wise Oxy-Hb β values (all p > 0.05). After the 6-week intervention, paired t-tests showed significant within-group increases in MMSE scores and prefrontal Oxy-Hb integral values in both groups (all p < 0.05). After adjusting for baseline values using ANCOVA, the observation group had significantly higher post-treatment MMSE scores and prefrontal Oxy-Hb integral values than the control group, indicating significant between-group treatment effects. Channel-wise two-way mixed-design ANOVA demonstrated significant group × time interaction effects in six fNIRS channels (CH7, CH8, CH14, CH32, CH40, and CH45) after FDR correction for multiple comparisons. These significant interactions indicated that the temporal trajectories of task-evoked cortical activation differed between the two groups. Conclusion The combination of iTBS and hyperbaric oxygen therapy may improve cognitive function in patients with post-stroke mild cognitive impairment; the increased task-related Oxy-Hb levels and prefrontal neural activation may reflect modulation of cerebral oxygen metabolism and cognitive network activity.