Non-invasive cervical vagus nerve stimulation effects on reaction time and valence image anticipation response

Abstract

Background: Norepinephrine (NE) driven noninvasive vagus nerve stimulation (nVNS), which improves attention and reduces reaction time, augments learning. Equally important, endogenous NE mediated arousal is highly dependent on the valence (positive or negative) of the exogenous stimulus. But to date, no study has measured valence specific effects of nVNS on both functional magnetic resonance imaging (fMRI) anticipation task response and reaction time in healthy individuals. Therefore, the aim of this pilot study was to assess whether nVNS vs sham modulates valence cortical anticipation task response and reaction time in a normative sample.

Methods: Participants received right sided transcutaneous cervical nVNS (N = 12) or sham (N = 12) stimulation during a 3T fMRI scan. Subjects first performed a continuous performance task (CPT) and then a cued anticipation task to images of positively and negatively valenced events during fMRI. Reaction times to cues and Blood oxygen level dependent (BOLD) response were examined over phase to identify effects of nVNS/sham over time.

Results: nVNS reduced reaction time for all valenced image anticipation trials. With the fMRI anticipation task, we observed a valence-specific effect; nVNS increased responsivity to images with negative valence and decreased responsivity to images with positive valence, whereas sham showed an inverse valence response.

Conclusions: nVNS was linked to reduced reaction time during the anticipation task. In tandem, nVNS consistently enhanced responsivity to negatively valenced images and diminished responsivity to positively valenced images, suggesting specific nVNS driven endogenous neurotransmitter signaling may contribute.

Keywords: Anticipation; Arousal; Attention; Cervical noninvasive vagal nerve stimulation; Functional magnetic resonance imaging; Locus coeruleus; Norepinephrine.

Figure 1.

Noninvasive Vagus Nerve Stimulation Study Design. Subjects were screened and randomized to either the sham treatment or nVNS group. Sham stimulation was carried out posteriolateral to the sternocleidomastoid. In the nVNS group, stimulation occurred anteromedial to the sternocleidomastoid and lateral to the trachea. 40 min after completion of stimulation (sham or nVNS), subjects participated in the functional magnetic resonance imaging anticipation task. This task combines a continuous performance task (CPT) with the interspersed presentation of affective stimuli. Subjects were asked to press a button based on a type of shape (circle or square). They were instructed that a green shape accompanied by a low pitch tone indicated a positive image would appear (6 sec). In contrast, a red shape accompanied by a high pitch tone signaled an impending negative image (6 sec). Images displayed (2 sec) in this paradigm were taken from the International Affective Picture System (IAPS) [59].

Figure 2.

Reaction time across phases (1–2) demonstrate a group*phase (p=.01) significant effect; the nVNS group showed greater reduction in reaction time over the duration (phase 1–2) of the image task when compared to sham for Continuous Performance Task (CPT), as well as for the positive and negative imagery. Reaction time for all image tasks over all phases (i.e., CPT, positive and negative, for phase 1–2) improved in the nVNS group. (+/− is reported as Standard Error, CPT=Continuous Performance Task, POS=positive image task, NEG=negative image task, nVNS=Non-invasive Vagus Nerve Stimulation, Sham=sham device, Phase 1=1^st 1/2^nd of task duration Phase 2=2/2^nd of task duration).

Figure 3.

Group*Valence*Phase analysis separated into 1^st (solid line) and 2^nd phase (dashed line) demonstrate left precentral gyrus, Broadman Areas (BA) 44, (A), and BA6 (D, H), left post central gyrus BA3 (K), left anterior insula BA13 (O) and left anterior cingulate BA32 (R), (p<.000001). During the valence anticipation task, Group*Valence*Phase analyses of negative imagery (red box) demonstrate nVNS phase 1 low response followed by consistent greater response during phase 2; in converse, sham stimulation response was greatest during phase 1, but decreased during phase 2 (B, E, I, L, P, S). During the valence anticipation task, Group*Valence*Phase analyses of positive imagery (green box) demonstrate nVNS initial phase 1 greater response followed by consistent low response during phase 2; in converse, sham stimulation response was low during phase 1, but increased significantly during phase 2 (C, F, J, M, Q, T) for all ROI.