title: Using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (fMRI) and dynamic causal modeling to understand the discrete circuit specific changes of medications: lamotrigine and valproic acid changes in motor or prefrontal effective connectivity.
abstract: The purpose of this study was to use interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) to investigate the effects of lamotrigine (LTG) and valproic acid (VPA) on effective connectivity within motor and corticolimbic circuits. In this randomized, double-blind, crossover trial, 30 healthy volunteers received either drug or placebo 3.5 h prior to interleaved TMS/fMRI. We utilized dynamic causal modeling (DCM) to assess changes in the endogenous effective connectivity of bidirectional networks in the motor-sensory system and corticolimbic circuit. Results indicate that both LTG and VPA have network-specific effects. When TMS was applied over the motor cortex, both LTG and VPA reduced TMS-specific effective connectivity between primary motor (M1) and pre-motor cortex (PMd), and between M1 and the supplementary area motor (SMA). When TMS was applied over prefrontal cortex, however, LTG alone increased TMS-specific effective connectivity between the left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulate cortex (ACC). In summary, LTG and VPA inhibited effective connectivity in motor circuits, but LTG alone increased effective connectivity in prefrontal circuits. These results suggest that interleaved TMS/fMRI can assess region- and circuit-specific effects of medications or interventions.
authors.affiliation: Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA. lixi@musc.edu
authors.forename: Xingbao
authors.initials: X
authors.lastname: Li
authors.forename: Charles H
authors.initials: CH
authors.lastname: Large
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ricci
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Taylor
authors.forename: Ziad
authors.initials: Z
authors.lastname: Nahas
authors.forename: Daryl E
authors.initials: DE
authors.lastname: Bohning
authors.forename: Paul
authors.initials: P
authors.lastname: Morgan
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology*; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D007839:Functional Laterality; D006801:Humans; D000077213:Lamotrigine; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D014227:Triazines / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine