BOLD fMRI activation induced by vagus nerve stimulation in seizure patients

Liu, Wen Ching; Mosier, Kristine M.; Kalnin, Andrew; Marks, David

doi:10.1136/jnnp.74.6.811

Cited by 76 publications

(56 citation statements)

References 12 publications

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“…In patient studies of acute VNS, local activations and deactivations were also reported (Bohning et al, 2001;Dietrich et al, 2008;Liu et al, 2003;Lomarev et al, 2002;Nahas et al, 2007;Narayanan et al, 2002;Sucholeiki et al, 2002). The differences between these findings and ours can be explained by several factors, such as diversity in stimulation protocols or in animal preparation.…”

Section: Discussionsupporting

confidence: 57%

“…This has been confirmed electrophysiologically by showing increases in neuronal firing rates in those structures after acute VNS (Groves et al, 2005) or after long-term stimulation treatment in rats (Dorr and Debonnel, 2006). In humans in vivo, central effects of VNS, usually performed at about 30 Hz, have been studied mostly using electroencephalography (EEG) (Marrosu et al, 2005), positron emission tomography (PET) and single photon emission computer tomography (SPECT) (see (Chae et al, 2003) for a review) and functional magnetic resonance imaging (fMRI) (Bohning et al, 2001;Dietrich et al, 2008;Liu et al, 2003;Lomarev et al, 2002;Nahas et al, 2007;Narayanan et al, 2002;Sucholeiki et al, 2002). Despite a significant variability in reported findings, activations in the medulla/brainstem, limbic regions (insula, anterior cingulate cortex, hippocampus, amygdala, and hypothalamus), thalamus, cerebellum, and periaqueductal grey (PAG) were most commonly observed.…”

Section: Introductionmentioning

confidence: 98%

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Dynamic Causal Modelling and physiological confounds: A functional MRI study of vagus nerve stimulation

et al. 2010

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Dynamic Causal Modelling (DCM) has been proposed to estimate neuronal connectivity from functional magnetic resonance imaging (fMRI) using a biophysical model that links synaptic activity to hemodynamic processes. However, it is well known that fMRI is sensitive not only to neuronal activity, but also to many other psychophysiological responses which may be task-related, such as changes in cardio-respiratory activity. They are not explicitly taken into account in the generative models of DCM and their effects on estimated neuronal connectivity are not known. The main goal of this study was to report the face validity of DCM in the presence of strong physiological confounds that presumably cannot be corrected for, using an fMRI experiment of vagus nerve stimulation (VNS) performed in rats. First, a simple simulation was used to evaluate the principled ability of DCM to recover directed connectivity in the presence of a confounding factor. Second, we tested the experimental validity using measures of the BOLD correlates of left 5Hz VNS. Because VNS mostly activates the central autonomic regulation system, fMRI signals were likely to represent both direct and indirect vascular responses to such activation. In addition to the inference of standard statistical parametric maps, DCM was thus used to estimate directed neural connectivity in a small brain network including the nucleus tractus solitarius (NTS) known to receive vagal afferents. Though blood pressure changes may constitute a major physiological confound in this dataset, model comparison of DCMs still allowed the identification of the NTS as the input station of the VNS pathway to the brain. Our study indicates that current developments of DCM are robust to psychophysiological responses to some extent, but does not exclude the need to develop specific models of brain - body interactions within the DCM framework to better estimate neuronal connectivity from fMRI time series.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 98%

Dynamic Causal Modelling and physiological confounds: A functional MRI study of vagus nerve stimulation

et al. 2010

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“…The parabrachial nucleus projects to the intralaminar nuclei of the thalamus, which in turn project widely to the cerebral cortex. Brain circuitry activated during VNS has been mapped in animals using c-fos expression as a marker [23], and in humans using positron-emission tomography scanning [10,[14][15][16], single photon emission computed tomography (SPECT) [25], and functional magnetic resonance imaging [8,18,22]. In these studies, the activated structures are predicted by the known central connections of the vagus nerve.…”

Section: Relevant Neuroanatomy Of Vnsmentioning

confidence: 99%

Therapeutic effects of vagus nerve stimulation in epilepsy and implications for sudden unexpected death in epilepsy

Schachter

2006

Clin Auton Res

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Vagus nerve stimulation (VNS) is a non-pharmacological therapy approved by the FDA for treatment of patients with partial-onset epilepsy. The most frequently encountered adverse effects typically occur during stimulation, are usually mild to moderate in severity, and resolve with reduction in current intensity or spontaneously over time. There are no apparent effects of VNS on vagally mediated visceral function. Though the precise mechanism of action of VNS remains unknown, available evidence suggests that central autonomic nervous system pathways are involved, which have also been implicated in sudden unexpected death in epilepsy (SUDEP). Studies to date of VNS and SUDEP are limited and do not conclusively show an association between VNS and SUDEP rates independent of other epilepsy-specific variables.

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“…A recent SPECT study suggested that 4 weeks of active VNS therapy in depression is associated with decreased activity in hippocampus and amygdala and increased activity in left prefrontal cortex (Zobel et al, 2005). Researchers have also used functional MRI (fMRI) to investigate VNS in epilepsy (Narayanan et al, 2002;Sucholeiki et al, 2002;Liu et al, 2003) and depression (Maniker et al, 2000;Bohning et al, 2001;Lomarev et al, 2002;Mu et al, 2004). Initial studies of depressed participants showed the feasibility of performing VNS-synchronized fMRI studies and compared the location and amount of blood oxygenation level dependent (BOLD) signal change caused by acute VNS for 7 s with the period when the device was not firing (Bohning et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Serial Vagus Nerve Stimulation Functional MRI in Treatment-Resistant Depression

Nahas

Tenebäck²,

Chae

et al. 2007

Neuropsychopharmacol

133

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Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, doubleblind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS.

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BOLD fMRI activation induced by vagus nerve stimulation in seizure patients

Cited by 76 publications

References 12 publications

Dynamic Causal Modelling and physiological confounds: A functional MRI study of vagus nerve stimulation

Dynamic Causal Modelling and physiological confounds: A functional MRI study of vagus nerve stimulation

Therapeutic effects of vagus nerve stimulation in epilepsy and implications for sudden unexpected death in epilepsy

Serial Vagus Nerve Stimulation Functional MRI in Treatment-Resistant Depression

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