Intervention Study Of The High-defifinition Transcranial Direct Current Stimulation In Patients With Prolonged Disorder Of Consciousness

Background:Disorder of consciousness(DOC)refers to the pathological state of severe motor and cognitive impairment caused by various causes.With the continuous development of the current medical technology,more patients with severe brain function impairment can continue to survive.The current increasing number of patients with prolonged disorders of consciousness(p DOC)poses a huge burden on their families and even on the medical system.The electrophysiological evidence supporting the therapeutic efficacy of high-definition transcranial direct current stimulation(HD-t DCS)sessions on consciousness improvement in patients with p DOC has not been firmly established.Objectives:To explore the behavioral effects of HD-t DCS on the left dorsolateral prefrontal lobe(dorsolateral prefrontal cortex,DLPFC)in p DOC patients,and to explore the functional connectivity changes in p DOC patients after HD-t DCS intervention to better explain the electrophysiological mechanisms of the effects of HD-t DCS on patients with p DOC.Method:Twenty two DOC patients were assigned to HD-t DCS stimulation.Each of them underwent the left DLPFC studies twice daily(10 times in total)of over five consecutive working days.The Coma Recovery Scale-Revised(CRS-R)scores evaluating the consciousness level and the rest-state electroencephalographic(EEG)were recorded before HD-t DCS,after the one sessions and after the ten sessions.And the patients were studied for a follow-up period of 3 months after stimulation.According to whether the CRS-R scores increased before and after stimulation,we divided these subjects into a responsive group and non-responsive group,and compared the differences in functional connectivity between the groups in different frequency bands and brain regions,as well the relationship between functional connectivity values and CRS-R scores and 3-month patient follow-up outcomes.All data were analyzed statistically using SPSS 23.0,where categorical variables in the responsive and non-responsive groups were compared using theX~2 test,normality distribution test for quantitative variables and comparative analysis using the independent sample t-test.Two-way repeated ANOVA was used to analyze the changes in Phase Locking Value(PLV)at different time points between the RE and N-RE groups.Finally,Spearman’s rank test correlation analysis was used to analyze the relationship between PLV changes and the increase in CRS-R scores of the DOC patients.Results:No adverse effects were observed in all of the patients,and none of them had a decrease in their CRS-R scores.Increases in CRS-R scores were observed in four patients after a single HD-t DCS stimulation,but were not statistically significant(t=-2.017,P=0.057).After five consecutive days of HD-t DCS stimulation,patients’CRS-R scores were significantly higher than before stimulation(t=-3.512,P=0.002).Furthermore,we observed significant improvement in all six subscales of CRS-R scale after repeated stimulation,including auditory(t=-3.480,P=0.002),visual(t=-2.569,P=0.018),motor(t=-2.614,P=0.016),verbal(t=-2.347,P=0.029),communication(t=-2.160,P=0.042),and arousal functions(t=-2.160,P=0.042).The change of PLV on the theta frequency band in the left-frontal-parietooccipital region was positively correlated with the change of CRS-R score(r=0.694,P=0.001).As the number of stimuli increased,we observed that in the responsive group,the change in PLV showed an upward trend,and the increase in the PLV appeared in the left-frontal-parietooccipital region at 4-8 Hz(t=4.525,P=0.0088)and in the intra-bifrontal region at 8-13 Hz(t=2.671,P=0.0481).In the non-responsive group,although the CRS-R score did not change after stimulation,the PLV showed a downward trend,and the decrease in the PLV appeared in the intra-bifrontal region at 8–13 Hz(t=4.004,P=0.0412).In addition,at three-month follow-up,patients with increased PLV in the intra-bifrontal region at 8–13 Hz(P=0.018)after repeated HD-t DCS stimulation had better outcomes than those without.Conclusion:Repeated anodal HD-t DCS of the left DLPFC produced clinically significant improvements in p DOC patients.The increase of functional connectivity in the brain regions may be associated with the improvement of related awareness after HD-t DCS and may be a predictor of better long-term outcomes.