title: Transcranial Direct Current Stimulation Post-Stroke Upper Extremity Motor Recovery Studies Exhibit a Dose-Response Relationship.
abstract: OBJECTIVE
  Transcranial direct current stimulation (tDCS) has shown mixed results in post-stroke motor recovery, possibly because of tDCS dose differences. The purpose of this meta-analysis was to explore whether the outcome has a dose-response relationship with various dose-related parameters.
  
  
  METHODS
  The literature was searched for double-blind, randomized, sham-controlled clinical trials investigating the role of tDCS (≥5 sessions) in post-stroke motor recovery as measured by the Fugl-Meyer Upper Extremity (FM-UE) scale. Improvements in FM-UE scores were compared between active and sham groups by calculating standardized mean differences (Hedge's g) to derive a summary effect size. Inverse-variance-weighted linear meta-regression across individual studies was performed between various tDCS parameters and Hedge's g to test for dose-response relationships.
  
  
  RESULTS
  Eight studies with total of 213 stroke subjects were included. Summary Hedge's g was statistically significant in favor of the active group (Hedge's g = 0.61, p = 0.02) suggesting moderate effect. Specifically, studies that used bihemispheric tDCS montage (Hedge's g = 1.30, p = 0.08) or that recruited chronic stroke patients (Hedge's g = 1.23, p = 0.02) showed large improvements in the active group. A positive dose-response relationship was found with current density (p = 0.017) and charge density (p = 0.004), but not with current amplitude. Moreover, a negative dose-response relationship was found with electrode size (p < 0.001, smaller electrodes were more effective).
  
  
  CONCLUSIONS
  Our meta-analysis and meta-regression results suggest superior motor recovery in the active group when compared to the sham group and dose-response relationships relating to electrode size, charge density and current density. These results need to be confirmed in future dedicated studies.
authors.affiliation: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Pratik Y
authors.initials: PY
authors.lastname: Chhatbar
authors.affiliation: Department of Public Health Science, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Ramakrishnan
authors.affiliation: Department of Health Science & Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Kautz
authors.affiliation: Ralph H. Johnson VA Medical Center, Charleston, SC, USA; Department of Psychiatry and Behavioral Science, Brain Stimulation Laboratory, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
authors.affiliation: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.affiliation: Department of Neurology, College of Medicine, Medical University of South Carolina, Charleston, SC, USA; Department of Health Science & Research, College of Health Professions, Medical University of South Carolina, Charleston, SC, USA. Electronic address: feng@musc.edu.
authors.forename: Wuwei
authors.initials: W
authors.lastname: Feng
mesh_terms: D000368:Aged; D006801:Humans; D020127:Recovery of Function; D020521:Stroke / Q000628:therapy; D000071939:Stroke Rehabilitation; D065908:Transcranial Direct Current Stimulation; D034941:Upper Extremity / Q000502:physiology*
keywords: Dose–response relationship; Hedge's g; Meta-analysis; Meta-regression; Motor recovery; Stroke; Transcranial direct current stimulation; tDCS