Elsevier

NeuroImage

Volume 54, Issue 1, 1 January 2011, Pages 380-388
NeuroImage

Technical Note
Striatal functional connectivity networks are modulated by fMRI resting state conditions

https://doi.org/10.1016/j.neuroimage.2010.07.021Get rights and content

Abstract

Resting state fluctuations in blood oxygenation level dependent functional connectivity magnetic resonance imaging (BOLD fcMRI) time-series have been increasingly employed to study functional connectivity networks in healthy and diseased brain. FcMRI studies have been conducted under a number of different conditions, including resting eyes open, visual fixation and finger tapping. BOLD fcMRI networks are believed to reflect both anatomically constrained spontaneous fluctuations and state-dependent activity. In this study, state-dependence of functional connectivity to dorsal and ventral striatum was assessed with fcMRI during an eyes open resting state condition (REST) and during continuous 3 Hz transcutaneous electrical nerve stimulation (TENS), with the a priori hypotheses: (1) dorsal striatum connectivity with sensorimotor/attention networks will be stronger during TENS compared to REST, (2) ventral striatum connectivity with limbic system emotion-processing network will be weaker during TENS compared to REST and (3) ventral striatum connectivity with sensorimotor/attention networks will be stronger during TENS compared to REST. These hypotheses were confirmed by the results obtained, indicating that resting state BOLD fMRI networks reflect, in substantial measure, state-dependent activity.

Introduction

Coherent resting state fluctuations in blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) data in functionally connected regions of the brain were first observed more than a decade ago (Biswal et al., 1995). Resting state fluctuations in BOLD fMRI time-series have been increasingly employed to study functional connectivity networks in healthy brain and in disease (Buckner et al., 2008, Fox & Raichle, 2007, Greicius, 2008, Williamson, 2007). Functional connectivity MRI (fcMRI) studies have been conducted under a number of different conditions: resting eyes open (Fox et al., 2005, Van Dijk et al., 2010, Yan et al., 2009), eyes closed (Fox et al., 2005, Greicius et al., 2009, Van Dijk et al., 2010, Yan et al., 2009), visual fixation (Buckner et al., 2009, Fox et al., 2005, Van Dijk et al., 2010, Yan et al., 2009), focal visual stimulation (Bianciardi et al., 2009a), viewing pictures with positive, negative or neutral valences (Anand et al., 2005), finger tapping (Morgan and Price, 2004), continuous performance tasks (Amann et al., 2009), tactile stimulation (Mantini et al., 2009) and acupuncture (Hui et al., 2009). A number of recent studies have explicitly studied the state dependence of different functional connectivity networks (Bianciardi et al., 2009a, Fransson, 2006, Hampson et al., 2002, Newton et al., 2007, Van Dijk et al., 2010, Yan et al., 2009).

BOLD fcMRI networks are believed to reflect both anatomically constrained spontaneous fluctuations and state-dependent activity (Buckner et al., 2009, Fox & Raichle, 2007). The intent of this study was to examine how functional connectivity in specific well-established brain networks is modulated by resting state condition. Classical studies (Drevets & Raichle, 1998, Price et al., 1996) reveal a reciprocal relationship between cognitive and emotion systems in the brain. The activation in dorsal and lateral aspects of the prefrontal cortex and the dorsal anterior cingulate increases during attention-demanding tasks compared to emotional tasks. Also, activation in these same areas decreases when an emotional component is added to the task. At the same time, activation in limbic areas involved in emotion processing, (such as ventral prefrontal cortex and ventral anterior cingulate) increases in emotion compared to attention-only tasks, and decreases during attention-demanding tasks. Attention and sensorimotor networks often show concomitant patterns of activation during sensory and attention tasks (Drevets & Raichle, 1998, Fan et al., 2005, Kim et al., 2006, Wenderoth et al., 2005a, Wenderoth et al., 2005b) and are often not distinguished from each other in animal literature (Haber et al., 1995, Neafsey, 1990, Ongur et al., 1998, Ongur & Price, 2000). In this study, we examined whether differences in sensory and attention demands of resting state conditions lead to analogous changes in functional connectivity in sensorimotor/attention networks and in emotion-processing networks.

The striatum receives projections from the entire cerebral cortex (Alexander et al., 1986, Alexander et al., 1990, Lawrence et al., 2000, Postuma & Dagher, 2006) and has rich connections to both sensorimotor/attention and limbic emotion-processing networks. Hence it can serve as an optimal seed region to assess reciprocal changes in functional connectivity in these two systems. The striatum can be divided into ventral striatum (VS) and dorsal striatum (DS), which are thought to be highly inter-connected regions with a dissociation of functions (Haber, 2003, Price et al., 1996, Voorn et al., 2004). The most superior aspect of the DS is strongly associated with sensorimotor experiences (Haber, 2003, Packard & Knowlton, 2002, White & McDonald, 2002) and more inferior aspects of the DS are associated with higher order cognitive functions such as attention (Voorn et al., 2004). VS is strongly connected to the limbic emotion processing system comprised of areas such as the amygdala, ventral anterior cingulate, ventromedial and ventrolateral prefrontal cortex, medial dorsal nucleus of the thalamus and hippocampus (Drevets & Raichle, 1998, Heidbreder & Groenewegen, 2003, Morgane et al., 2005, Price et al., 1996). Intra-striatal connections are asymmetric, with significantly more VS efferents to DS and sensorimotor and attention networks than DS efferents to VS and the limbic system (Joel and Wiener, 2000). VS acts as an interface between emotion processing and sensorimotor/attention systems (Haber et al., 1995, Ongur et al., 2003) and can be recruited in sensorimotor paradigms.

Transcutaneous electrical nerve stimulation (TENS) has been shown to activate areas that are part of sensorimotor and/or attention networks, including primary and secondary somatosensory cortex, insula, premotor and motor cortex, supplementary motor area (SMA), dorsal anterior cingulate, dorsolateral prefrontal cortex, paracentral lobule, parietal lobe, thalamus, basal ganglia and cerebellum (Arienzo et al., 2006, Ferretti et al., 2007, Fors et al., 1996, Huang et al., 2010, Pleger et al., 2003, Porro et al., 2004). TENS can also be controlled by the experimenter without being confounded by subject task performance (e.g. as in finger-tapping). Thus TENS provides a convenient and controllable way to stimulate these networks. In this study, changes in striatal functional connectivity networks were examined during an eyes open resting (REST) condition compared to a continuous transcutaneous electrical median nerve stimulation that was not painful. The a priori hypotheses in this study were: (1) the DS connectivity to sensorimotor/attention areas involved in median nerve stimulation will be higher during TENS compared to REST, (2) the VS connectivity to limbic system emotion processing areas will be higher during REST compared to TENS and (3) the VS connectivity to sensorimotor/attention areas involved in median nerve stimulation will be higher during TENS compared to REST. Confirmation of the a priori hypotheses would add evidence to the notion that resting state BOLD fMRI networks reflect, in substantial measure, state-dependent activity.

Section snippets

Subjects

Thirteen healthy subjects (5 F, 8 M, mean age 32 years, all right-handed, mean education 17 years) participated. Written informed consent was obtained for all subjects.

Task description

Each subject performed fcMRI scans under the following three resting state conditions.

  • (1)

    Resting eyes open with transcutaneous median nerve stimulation: For the TENS condition, the subjects were asked to lie motionless in the scanner with their eyes open. Continuous transcutaneous electrical median nerve stimulation that was not

Results and Discussion

All subjects were able to keep their eyes open for the duration of all fcMRI runs as ascertained by exit interviews. The maximal displacement calculated from estimated motion parameters was within one voxel in all the runs for all subjects. The MBPM power spectra from all subjects were similar to those obtained by other groups (Shmueli et al., 2007), with the spectral power of heart rate variability concentrated at low frequencies (below 0.03 Hz). The individual subject RVT power spectra were

Conclusion

This study confirms the hypothesis of a reciprocal relationship between the functional connectivity of the striatum within sensorimotor/attention networks, on the one hand, and emotion-processing network on the other. During TENS, there were increases in the strength of connections between the dorsal striatum and sensorimotor/attention networks, together with a concomitant decrease in the strength of the connectivity of the ventral striatum to the limbic emotion-processing network. The results

Acknowledgments

This study was supported by DoD grant no. DAMD 17-01-1-0741 from the U.S. Army Medical Research and Materiel Command and by VA IDIQ contract number VA549-P-0027 awarded and administered by the Dallas, TX VA Medical Center. The content of this paper does not necessarily reflect the position or the policy of the U.S. government, and no official endorsement should be inferred. Construction of the TENS stimulation device was supported by the University of Texas Southwestern Medical Center Mobility

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