title: Spinal Cord Stimulation (SCS) and Functional Magnetic Resonance Imaging (fMRI): Modulation of Cortical Connectivity With Therapeutic SCS.
abstract: BACKGROUND
  The neurophysiological basis of pain relief due to spinal cord stimulation (SCS) and the related cortical processing of sensory information are not completely understood. The aim of this study was to use resting state functional magnetic resonance imaging (rs-fMRI) to detect changes in cortical networks and cortical processing related to the stimulator-induced pain relief.
  
  
  METHODS
  Ten patients with complex regional pain syndrome (CRPS) or neuropathic leg pain underwent thoracic epidural spinal cord stimulator implantation. Stimulation parameters associated with "optimal" pain reduction were evaluated prior to imaging studies. Rs-fMRI was obtained on a 3 Tesla, Philips Achieva MRI. Rs-fMRI was performed with stimulator off (300TRs) and stimulator at optimum (Opt, 300 TRs) pain relief settings. Seed-based analysis of the resting state functional connectivity was conducted using seeds in regions established as participating in pain networks or in the default mode network (DMN) in addition to the network analysis. NCUT (normalized cut) parcellation was used to generate 98 cortical and subcortical regions of interest in order to expand our analysis of changes in functional connections to the entire brain. We corrected for multiple comparisons by limiting the false discovery rate to 5%.
  
  
  RESULTS
  Significant differences in resting state connectivity between SCS off and optimal state were seen between several regions related to pain perception, including the left frontal insula, right primary and secondary somatosensory cortices, as well as in regions involved in the DMN, such as the precuneus. In examining changes in connectivity across the entire brain, we found decreased connection strength between somatosensory and limbic areas and increased connection strength between somatosensory and DMN with optimal SCS resulting in pain relief. This suggests that pain relief from SCS may be reducing negative emotional processing associated with pain, allowing somatosensory areas to become more integrated into default mode activity.
  
  
  CONCLUSIONS
  SCS reduces the affective component of pain resulting in optimal pain relief. Study shows a decreased connectivity between somatosensory and limbic areas associated with optimal pain relief due to SCS.
authors.affiliation: Department of Neurosurgery, Center of Neuromodulation, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Milind
authors.initials: M
authors.lastname: Deogaonkar
authors.affiliation: Department of Neurosurgery, Center of Neuromodulation, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Mayur
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Neurosurgery, Children's National Medical Center, Washington, DC, USA.
authors.forename: Chima
authors.initials: C
authors.lastname: Oluigbo
authors.affiliation: Department of Psychology, The Ohio State University, Columbus, OH, USA.
authors.forename: Dylan M
authors.initials: DM
authors.lastname: Nielson
authors.affiliation: Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Neuromodulation Research, Medtronic Inc., Minneapolis, MN, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Vera-Portocarrero
authors.affiliation: Neuromodulation Research, Medtronic Inc., Minneapolis, MN, USA.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Molnar
authors.affiliation: Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Abduljalil
authors.affiliation: Department of Psychology, The Ohio State University, Columbus, OH, USA.
authors.forename: Per B
authors.initials: PB
authors.lastname: Sederberg
authors.affiliation: Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Knopp
authors.affiliation: Department of Neurosurgery, Center of Neuromodulation, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Rezai
mesh_terms: D000328:Adult; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000502:physiology*; D020918:Complex Regional Pain Syndromes / Q000628:therapy*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology*; D009437:Neuralgia / Q000628:therapy*; D062187:Spinal Cord Stimulation
keywords: Connectivity; functional MRI; neural networks; neuromodulation; neuropathic pain