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

• Published in: Psychiatry research. Neuroimaging Vol. 194; no. 2; pp. 141 - 148
• Main Authors: Li, Xingbao, Large, Charles H, Ricci, Raffaella, Taylor, Joseph J, Nahas, Ziad, Bohning, Daryl E, Morgan, Paul, George, Mark S
• Format: Journal Article
• Language: English; French
• Published: Shannon Elsevier Ireland Ltd 30.11.2011; Elsevier
• Subjects: Adolescent; Adult; Anticonvulsants - pharmacology; Biological and medical sciences; Brain Mapping; Cerebral Cortex - blood supply; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Cross-Sectional Studies; Double-Blind Method; Dynamic causal modeling; Functional Laterality; Humans; Lamotrigine; Magnetic Resonance Imaging - methods; Male; Medical sciences; Models, Neurological; Network; Neural Pathways - blood supply; Neural Pathways - drug effects; Neural Pathways - physiology; Neuroimaging; Neuropharmacology; Pharmacology. Drug treatments; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Radiology; Transcranial magnetic stimulation; Transcranial Magnetic Stimulation - methods; Triazines - pharmacology; Valproic acid; Valproic Acid - pharmacology; Young Adult; Neuroimaging; Transcranial magnetic stimulation; Dynamic causal modeling; Valproic acid; Network; Lamotrigine; Psychotropic; Central nervous system; Anticonvulsant; Encephalon; Mood stabilizer; Functional magnetic resonance imaging; Dynamic model; Human; 4-Aminobutyrate transaminase; Enzyme; Transferases; Enzyme inhibitor; Prefrontal cortex; Nuclear magnetic resonance imaging; Histone deacetylase inhibitor; Treatment; Transaminases; Triazine derivatives; Medical imagery; Causality; Functional imaging
• ISSN: 0925-4927; 1872-7506
• DOI: 10.1016/j.pscychresns.2011.04.012

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 both 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.