title: MRI-constrained spectral imaging of benzodiazepine modulation of spontaneous neuromagnetic activity in human cortex.
abstract: Spontaneous electromagnetic brain rhythms have been widely used in human neuropharmacology, but their applicability is complicated by the difficulties to localize their origins in the human cortex. Here, we used a novel multi-modal non-invasive imaging approach to localize lorazepam (30 microg/kg i.v.) modulation of cortical generators of spontaneous brain rhythms. Eight healthy subjects were measured with 306-channel magnetoencephalography (MEG) in a double-blind, randomized, placebo-controlled (saline), crossover design. For anatomically realistic source modeling, wavelet-transformed MEG data were combined with high-resolution MRI to constrain the current locations to the cortical mantle, after which individual data were co-registered to surface-based coordinate system for the calculation of group statistical parametric maps of drug effects. The distributed MRI-constrained MEG source estimates demonstrated decreased alpha (10 Hz) activity in and around the parieto-occipital sulcus and in the calcarine sulcus of the occipital lobe, following from increased GABA(A)-inhibition by lorazepam. Anatomically constrained spectral imaging displays the cortical loci of drug effects on oscillatory brain activity, providing a novel tool for human pharmacological neuroimaging.
authors.affiliation: Massachusetts General Hospital/Massachusetts Institute of Technology/Harvard Medical School-Athinoula A. Martinos Center for Biomedical Imaging, CNY149 13th Street, Charlestown, MA 02129, USA. jyrki@nmr.mgh.harvard.edu
authors.forename: Jyrki
authors.initials: J
authors.lastname: Ahveninen
authors.forename: Fa-Hsuan
authors.initials: FH
authors.lastname: Lin
authors.forename: Reetta
authors.initials: R
authors.lastname: Kivisaari
authors.forename: Taina
authors.initials: T
authors.lastname: Autti
authors.forename: Matti
authors.initials: M
authors.lastname: Hämäläinen
authors.forename: Steven
authors.initials: S
authors.lastname: Stufflebeam
authors.forename: John W
authors.initials: JW
authors.lastname: Belliveau
authors.forename: Seppo
authors.initials: S
authors.lastname: Kähkönen
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male
chemical_list: D018757:GABA Modulators; D008140:Lorazepam