Recent advances in the treatment of patients with

Recent advances in the treatment of patients with disorders of consciousness: a review of transcranial direct current stimulation efficacy Alice Barra 1, Géraldine Martens 1, Steven Laureys 1, Aurore Thibaut 1 1 Coma Science Group, GIGA Consciousness - GIGA Research, University of Liège, Belgium a. barra@uliege. be

AIM of STUDY Disorders of consciousness (DOC) challenging for treatment Transcranial direct-current stimulation (t. DCS) promising tool • Responders but • Effect duration • Best target Unclear: METHODS Review of t. DCS-based clinical trials in patients with DOC Inclusion criteria • randomized double-blind shamcontrolled trials • t. DCS as therapeutic intervention • Coma Recovery Scale-Revised • population of patients with DOC • articles in English. Comparing • effect sizes (independent samples Cohen’s d) • numbers of responders (twosample proportion test)

RESULTS Author and year Nbr of Time Sample Number Effect sessions since size of publication Left DLPFC most onset respond ers frequent target (5/8) with effect size from 0, 30 to 2, 22 Average effect size : repeated session (0, 75) vs single session (0, 20) Number of responders: repeated session (39/110) vs single session (22/111) (p=0. 0125) Target area 1. Thibaut et al. , 2014 Left DLPFC (F 3) 2. Martens et al. , (Submitted 2018) Primary motor (C 3 or C 4) Frontoparieta 3. Martens et al. , l network (In Prep 2018) (F 3, F 4, CP 5, CP 6) 15/55 0. 38 1 9 months N=10 4 UWS 6 MCS 1/10 0. 12 1 N=46 38 months 17 UWS 23 MCS 6/46 0. 12 5/13 0. 30 1 4. Estraneo et al. , 2017 Left DLPFC (F 3) 5 3 months N=13 7 UWS 6 MCS 5. Huang et al. , 2017 Posterior Parietal (Pz) 5 5 months N=33 33 MCS 9/33 0. 31 6. Martens et al. , Left DLPFC 2018 (F 3) 20 9 years N=22 22 MCS 6/22 0. 53 3 months N=16 16 MCS 9/16 0. 43 10/26 2. 22 7. Thibaut et al. , 2017 Figure 1: Visualization of targets effectiveness 36 months N=55 25 UWS 30 MCS 8. Zhang et al. , 2017 Left DLPFC (F 3) 5 N=26 Table 1: Articles and data included 10 5 months 11 UWS 15 MCS

CONCLUSIO NS DLPFC seems to be the most effective & promising target Repeated sessions of t. DCS seem to be more effective than single session t. DCS Individual responsiveness to t. DCS is still a key issue only subgroup of metabolic & atrophic individual diff MCS responded to t. DCS REFERENC Need to develop patient-tailored MRI-guided stimulation protocols ES 1. 2. 3. 4. 5. 6. 7. 8. 9. Thibaut A, et al. t. DCS in patients with disorders of consciousness; sham-controlled double-blind study. Neurology, 2014; 82: 1112 -8 Martens G, et al. Network- based stimulation in patients with severe brain injury: a tdcs-EEG randomized controlled trial. In preparation (2018) Martens G, et al. t. DCS targeting the motor cortex does not influence behavioural responsiveness in patients with DOC. Submitted (2018) Estraneo A, et al. Repeated transcranial direct durrent stimulation in prolonged disorders of consciousness: a double blind cross-over study. Jour or Neurol Sc, 2017; 375: 464 -470 Huang W, et al. Repeated stimulation of the posterior parietal cortex in patients in minimally conscious state: A sham-controlled randomized clinical trial, Brain Stimulation (2017); 1 -3 Martens G, et al. Randomized controlled trial of home-based 4 weeks t. DCs in chronic minimally conscious state. Brain Stimulation. 2018; 11(5): 982 -990 Thibaut A et al. Clinical response to Tdcs depends on residual brain metabolism and grey matter integrity in patients in a minimally conscious state. Brain stim, 2015; 8: 1116 -1123 Thibaut A, et al. Controlled clinical trial of repeated prefrontal t. DCS in chronic patients in minimally conscious state. Brain Injury, 2017; 31 (4) 466 Zhang Y, et al. Transcranial direct current stimulation in patients with prolonged disorders of consciousness: combined behavioural and event-related potential evidence. Front of Neurol, 2017; 8: 620

Thank you! Alice Barra 1, Géraldine Martens 1, Steven Laureys 1, Aurore Thibaut 1 1 Coma Science Group, GIGA Consciousness - GIGA Research, University of Liège, Belgium a. barra@uliege. athibaut@uliege. be