A VBM study demonstrating ‘apparent’ effects of a single dose of medication on T1-weighted MRIs

Structural Overlays

Axial Sections . Sagittal Sections . Coronal Sections

Structural & Perfusion Overlays

Axial Sections . Sagittal Sections . Coronal Sections
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Correction

SPM8 was used for brain analyses, not SPM7 as indicated in the publication.

Abstract

AUTHORS: Teresa R. Franklin, Ph.D.a, Ze Wang, Ph.D.a, Joshua Shin B.S.a, Kanchana Jagannathan M.S.a, Jesse J. Suh, Psy.D.a, d, John A. Detre, M.D.b, c, Charles P. O'Brien M.D., Ph.D.a, d, Anna Rose Childress, Ph.D.a, d

aDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA
bDepartment of Radiology, University of Pennsylvania, Philadelphia, PA
cDepartment of Neurology, University of Pennsylvania, Philadelphia, PA
dPhiladelphia VA Medical Center, Philadelphia, PA

ABSTRACT

Voxel-based morphometry (VBM) studies have interpreted longitudinal medication- or behaviorally-induced changes observed on T1-weighted magnetic resonance images (MRIs) as changes in neuronal structure. Although neurogenesis or atrophy certainly occurs, the use of T1-weighted scans to identify change in brain structure in vivo in humans has a vulnerability: the T1 relaxation time for arterial blood and gray matter are not clearly distinguishable and therefore, apparent reported structural findings might be at least partially related to changes in blood flow or other physiological signals. To examine the hypothesis that apparent structural modifications may reflect changes introduced by additional mechanisms irrespective of potential neuronal growth/atrophy, we acquired a high resolution T1-weighted structural scan and a 5-minute perfusion fMRI scan (a measurement of blood flow), prior to and after administration of an acute pharmacological manipulation, In a within subjects design, 15 subjects were either un-medicated or were administered a 20 mg dose of baclofen (an FDA-approved anti-spastic) approximately 110 minutes prior to acquiring a T1-weighted scan and a pseudo continuous arterial spin labeled (pCASL) perfusion fMRI scan. Using diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) within SPM8 we observed macroscopic, and therefore implausible, baclofen-induced decreases in VBM ‘gray matter’ signal in the dorsal rostral anterior cingulate [Family-wise error (FWE) corrected at p < 0.04, T= 6.54, extent: 1460 voxels] that overlapped with changes in blood flow. Given that gray matter reductions are unlikely following a single dose of medication these findings suggest that changes in blood flow are masquerading as reductions in gray matter on the T1-weighted scan irrespective of the temporal interval between baseline measures and longitudinal manipulations. These results underscore the crucial and immediate need to develop in vivo neuroimaging biomarkers for humans that can uniquely capture changes in neuronal structure dissociable from those related to blood flow or other physiological signals.