Multi-Target and Multi-Session Transcranial Direct Current Stimulation in Patients With Prolonged Disorders of Consciousness: A Controlled Study

Abstract

Objectives: To investigate the effect of multi-session transcranial direct current stimulation (tDCS) over the prefrontal area, left dorsolateral prefrontal cortex (DLPFC), and bilateral fronto-temporo-parietal cortices (FTPCs) in patients with prolonged disorders of consciousness (DOC) and to examine the altered cortical interconnections using non-linear electroencephalography (EEG).Methods: In this open-label controlled study, conventional treatments were implemented in both the control and tDCS groups, together with 80 tDCS sessions only in the tDCS group. The order of tDCS targets was as follows: prefrontal area, left FTPC, right FTPC, and left DLPFC. The Coma Recovery Scale-Revised (CRS-R) and non-linear EEG index were evaluated before and after the treatment. Additionally, the modified Glasgow Outcome Scale (mGOS) was used as a follow-up evaluation at 12 months after the disease onset.Results: The CRS-R improved significantly in both groups after the treatment. However, the CRS-R and mGOS were more significantly improved in the tDCS group than in the control group. Among the cross approximate entropy (C-ApEn) indices, the local CA-PA and CA-FA under the affected painful stimulus condition and all local and remote indices of the unaffected side under the unaffected painful stimulus condition were significantly higher in the tDCS group than in the control group. Multivariate logistic regression analysis revealed that group and type were the main relevant factors based on mGOS improvement. Multivariate linear regression analysis revealed that group, CA-FA, and CU-MTU were the main relevant factors based on CRS-R improvement under the affected painful stimulus conditions, whereas only CU-MTU and CU-FPU were relevant under the unaffected painful stimulus condition.Conclusion: Multi-target and multi-session tDCS could improve the cortical connections between the primary sensorimotor and frontal cortices of the affected hemisphere and the prefrontal-parietal and temporo-parietal associative cortical networks of the unaffected hemisphere. Thus, this tDCS protocol may be used as an add-on treatment for prolonged DOC.

tDCS-EEG for Predicting Outcome in Patients With Unresponsive Wakefulness Syndrome

“…Another study by our group assessing psychomotor inhibition state (PIS) after TBI in cases who recovered from UWS showed that multi-target (prefrontal area, left DLPFC) anodal tDCS could improve PIS . Furthermore, our most recent study confirmed that multitarget tDCS [prefrontal area, left DLPFC and bilateral frontotemporo-parietal cortices (FTPCs)] could overall improve the prognosis of DOC patients and the prognosis of patients in tDCS group (12/29, UWS to MCS) was significantly better than that in the control group (4/28, UWS to MCS) (Zhang et al, 2021). The above results suggest that multi-target tDCS combined with EEG (tDCS-EEG) is a promising method for predicting the prognosis of UWS patients.…”

“…Many studies and our previous studies have found that prefrontal-parietal cortical networks plays a critical role in improvement in patients with UWS (Cavinato et al, 2015(Cavinato et al, , 2019Naro et al, 2016a,b;Bai et al, 2017a,c;Cacciola et al, 2019;Zhang et al, 2021). The application of active tDCS on OFC can improve the level of consciousness by improving the residual connectivity between prefrontal lobe and motor area (Naro et al, 2015).…”

“…Chen's research also showed that stimulating multiple cortical areas rather than a single area is more meaningful for rehabilitation (Chen et al, 2019). Similarly, our recent study focused on the efficacy of multi-target and multi-session tDCS in patients with DOC (Zhang et al, 2021). Therefore, we optimized the treatment strategy in this study, applying multi-target tDCS to the prefrontal area, bilateral FTPCs and left DLPFC in patients with UWS.…”

Alteration of network connectivity in stroke patients with apraxia of speech after tDCS: A randomized controlled study

“…A higher C-ApEn value indicated more cortical interconnections ( 41 ). The expression formula and parameters had been described in our previous studies ( 33 , 40 ).…”

“…Among possible non-linear dynamics measures, cross approximate entropy (C-ApEn) was used to analyze two related time series and measure their degree of asynchrony by comparing sequences from one series to those of the second series to reflect the spatial decorrelation of cortical potentials from two remote sites ( 32 ). Our previous study showed that the EEG non-linear index of C-ApEn revealed altered cortical interconnections after tDCS treatment in patients with prolonged disorders of consciousness ( 33 ). As the EEG examination is easy to operate and the word repetition tasks during EEG can be completed within a short time, EEG is a suitable tool for dynamically observing network activity in research and clinical practice.…”