Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS)

Abstract

Both resting state functional magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS) are increasingly popular techniques that can be used to non-invasively measure brain connectivity in human subjects. TMS shows additional promise as a method to manipulate brain connectivity. In this review we discuss how these two complimentary tools can be combined to optimally study brain connectivity and manipulate distributed brain networks. Important clinical applications include using resting state fcMRI to guide target selection for TMS and using TMS to modulate pathological network interactions identified with resting state fcMRI. The combination of TMS and resting state fcMRI has the potential to accelerate the translation of both techniques into the clinical realm and promises a new approach to the diagnosis and treatment of neurological and psychiatric diseases that demonstrate network pathology.

Copyright © 2012 Elsevier Inc. All rights reserved.

Figures

Figure 1

Connectivity between the motor cortices assessed with resting state functional connectivity MRI and dual-coil stimulation with TMS. The top panel shows fMRI activation in response to a right hand button press (A), a left somatomotor region of interest (B), resting state functional connectivity with this left somatomotor cortex region of interest (C), a right somatomotor cortex region of interest defined on the basis of the resting state functional connectivity (D), and spontaneous fluctuations recorded in the left (pink line) and right (blue line) somatomotor cortices during the resting state conditions showing significant interhemispheric correlation (modified with permission from (Fox, Snyder et al. 2007)). The lower panel shows the effect of transcallosal inhibition using dual-coil TMS. When a conditioning pulse is delivered to the left motor cortex 8 ms before the test pulse is delivered to the right motor cortex the motor evoked potential recorded from the left hand is significantly decreased (modified with permission from (Kobayashi and Pascual-Leone 2003)).

Figure 2

Functional connectivity between the left dorsal lateral prefrontal cotex (DLPFC, yellow arrows) and ventral medial prefrontal cortex (yellow circles) assessed with TMS/Imaging and resting state functional connectivity MRI. A) Regional CBF changes assessed with PET in response to double-pulse TMS to the left DLPFC (modified with permission from (Paus, Castro-Alamancos et al. 2001)). B) BOLD changes assessed with fMRI in response to 1 Hz TMS to the left DLPFC (modified with permission from (Li, Nahas et al. 2004)). C) Dopamine release (decreases in [11C]FLB 457 binding potential) in response to 10 Hz TMS to the left DLPFC (modified with permssion from (Cho and Strafella 2009)). D) Anticorrelated networks identified using resting state functional connectivity MRI based on correlations within a system and negative corelations between systems (modified with permission from (Fox, Snyder et al. 2005)).

Figure 3

Using resting state fcMRI to target therapeutic TMS. A) TMS targets in the left dorsal lateral prefrontal cortex (DLPFC) known to be more effective (left) versus less effective (right) at producing an antidepressant response. B) Resting state functional connectivity reveals that the more effective target is more negatively correlated (anticorrelated) with the subgenual (inset) compared to the less effective target. C) Resting state BOLD time course extracted from the subgenual. D) Resting state functional connectivity identifies a theoretically optimal stimulation target in the left DLPFC based on anticorrelation with the subgenual. (Modified from (Fox, Buckner et al. 2012))

Figure 4

Modulating resting state functional connectivity networks using TMS. Both inhibitory and excitatory TMS were applied to the left inferior parietal lobule, part of the default mode network (top row). Inhibitory TMS resulted in pronounced increases in functional connectivity between the stimulation site and the medial temporal lobe (middle row) while excitatory TMS resulted in decreased correlation between the stimulation site and other nodes of the default mode network (bottom row). (Modified from (Eldaief, Halko et al. 2011)).