Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients
Authors: Marco Aiello
Aurore Thibaut
Charlotte Martial
Steven Laureys
Carol Di Perri
Enrico Amico
Andrea Soddu
Carlo Cavaliere
Journal: Frontiers in Cellular Neuroscience (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: disorders of consciousness; magnetic resonance imaging; minimally conscious state; prefrontal cortex; resting state networks
Affiliations: Coma Science Group, GIGA-Research, University and University Hospital of LiegeLiege, Belgium; NAPLab, IRCCS SDN Istituto di Ricerca Diagnostica e NucleareNaples, Italy., NAPLab, IRCCS SDN Istituto di Ricerca Diagnostica e Nucleare Naples, Italy., Coma Science Group, GIGA-Research, University and University Hospital of Liege Liege, Belgium., Coma Science Group, GIGA-Research, University and University Hospital of LiegeLiege, Belgium; Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital/Harvard Medical SchoolBoston, MA, USA., Department of Physics and Astronomy, Brain and Mind Institute, Western University London, ON, Canada.

Abstract:  Transcranial direct current stimulation (tDCS) is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS) patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions exist, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI) of 16 sub-acute and chronic MCS patients (6 tDCS responders) who successively received a single left dorsolateral prefrontal cortex (DLPFC) tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network (ECN) and default-mode network (DMN) was performed. tDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders (NR) MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus. Our findings suggest that a prior high connectivity with regions belonging to ECN can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS. 

Retracted: No

PubPeer comments:
 It is a bit unfortunate that in the statistical procedure you indicate this: The results were considered statistically significant under p 0.05 family wise error (FWE) corrected at cluster level, with clusters made of voxels surviving a p 0.01 with minimum cluster extent of 50 voxels. As known for many years and recently redemonstrated by [Eklund et al. 2016] , a cluster-forming threshold of .01 is NOT advisable. In so doing you are dangerously increasing the risk of false positives when performing cluster level inference. Could you elaborate on this? And what were the results like when using an approved .001 cluster-forming threshold? On a side note, thresholding the cluster size at 50 voxels has no statistical ground (with the information provided in the article) and seems to be purely for cosmetic reason. Could you comment on that? ,