title: Mapping effective connectivity in the human brain with concurrent intracranial electrical stimulation and BOLD-fMRI.
abstract: Understanding brain function requires knowledge of how one brain region causally influences another. This information is difficult to obtain directly in the human brain, and is instead typically inferred from resting-state fMRI.
  
  
  
  Here, we demonstrate the safety and scientific promise of a novel and complementary approach: concurrent electrical stimulation and fMRI (es-fMRI) at 3T in awake neurosurgical patients with implanted depth electrodes.
  
  
  
  We document the results of safety testing, actual experimental setup, and stimulation parameters, that safely and reliably evoke activation in distal structures through stimulation of amygdala, cingulate, or prefrontal cortex. We compare connectivity inferred from the evoked patterns of activation with that estimated from standard resting-state fMRI in the same patients: while connectivity patterns obtained with each approach are correlated, each method produces unique results. Response patterns were stable over the course of 11min of es-fMRI runs. COMPARISON WITH EXISTING METHOD: es-fMRI in awake humans yields unique information about effective connectivity, complementing resting-state fMRI. Although our stimulations were below the level of inducing any apparent behavioral or perceptual effects, a next step would be to use es-fMRI to modulate task performances. This would reveal the acute network-level changes induced by the stimulation that mediate the behavioral and cognitive effects seen with brain stimulation.
  
  
  
  es-fMRI provides a novel and safe approach for mapping effective connectivity in the human brain in a clinical setting, and will inform treatments for psychiatric and neurodegenerative disorders that use deep brain stimulation.
authors.affiliation: Department of Neurosurgery, Human Brain Research Laboratory, University of Iowa, Iowa City, IA 52241, USA. Electronic address: hiroyuki-oya@uiowa.edu.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oya
authors.affiliation: Department of Neurosurgery, Human Brain Research Laboratory, University of Iowa, Iowa City, IA 52241, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Howard
authors.affiliation: Department of Radiology, University of Iowa College of Medicine, Iowa City, IA 52241, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Magnotta
authors.affiliation: Department of Electrical and Computer Engineering, University of Iowa College of Engineering, USA.
authors.forename: Anton
authors.initials: A
authors.lastname: Kruger
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Griffiths
authors.affiliation: UCL Institute of Neurology, University College London, London, UK.
authors.forename: Louis
authors.initials: L
authors.lastname: Lemieux
authors.affiliation: UCL Institute of Child Health, University College London, London, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Carmichael
authors.affiliation: Institute of Neuroscience, Newcastle University, Newcastle, UK.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Petkov
authors.affiliation: Department of Neurosurgery, Human Brain Research Laboratory, University of Iowa, Iowa City, IA 52241, USA.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Department of Neurosurgery, Human Brain Research Laboratory, University of Iowa, Iowa City, IA 52241, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Kovach
authors.affiliation: Department of Neurosurgery, Human Brain Research Laboratory, University of Iowa, Iowa City, IA 52241, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sutterer
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Adolphs
mesh_terms: D000328:Adult; D001703:Biophysics; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000502:physiology; D001931:Brain Mapping; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Amygdala; DBS; Effective connectivity; Electrical stimulation; Functional MRI; Human