Vagal Nerve Stimulation (VNS) has been shown to significantly improve memory and performance of cognitive tasks in both rats and humans. It has also served as an FDA approved medical treatment for epilepsy and depression for over two decades. VNS has been shown to activate regions of the brain that serve as hotspots for epilepsy, including the hippocampus and amygdala. These regions of the brain are also known to be critically important for learning and comprehension, as well as cognition generally. Likewise, the vagal nerve has direct connections with the locus coeruleus (LC). The LC is the brain’s primary norepinephrine nucleus and regulates wakefulness, arousal, attention, and is involved in learning. All of these aspects of cognition are negatively affected by fatigue. Human subjects receiving VNS have shown specific enhancements in comprehension, leading to enhanced decision making. In addition, VNS has been shown to increase neuronal plasticity in humans. In small animal models, VNS has been shown to enhance decision making compared to animals receiving sham stimulation as evidence suggests that it augments plasticity in the brain in general.
The main goal of this study was to evaluate the efficacy of tVNS to mitigate the effects of fatigue induced by sleep deprivation on aspects of cognition including attention, arousal, multitasking, and memory in populations of Department of Defense (DoD) subjects. The primary objective was to demonstrate a >20% improvement in at least one cognitive skill during sleep deprivation stress when compared to the control population. The secondary objective was to assess effects of tVNS on subjective mood.
Two groups of participants with twenty in each group completed the procedures of this study. One group received either non-invasive tVNS over the left and right cervical vagal nerve (neck), or sham tVNS at 1900 hours during 34 hours of sustained wakefulness. Every three hours throughout the night, until 1700 the next day, participants completed a battery of cognitive tasks and subjective mood questionnaires. The task battery included the Mackworth Clock Test (Sustained Attention Task), the N-Back working memory task, the Psychomotor Vigilance Task (PVT), and the Air Force-Multi-Attribute Task Battery (AF-MATB). The Mood Questionnaire was a 15-item mood questionnaire where the participants checked a box closer to the mood on the scale that they most identified with at the moment. For example, “Fatigued or Energized,” “Happy or Sad,” and “Optimistic and Pessimistic” were items on this questionnaire. Depending on the box selected, the questionnaire would output a numerical score (1-7) to quantify the mood.
The purpose of this study was to investigate the use of peripheral nerve stimulation on the cervical vagus as a fatigue countermeasure. One of the primary findings from this study was a significant interaction for the multi-tasking test that occurred later in the testing at the 0700 and 1000 sessions. Participants had been awake for 24 to 27 hours during these two testing sessions, respectively, which represents a traditional low point for circadian rhythms; further analysis showed that the group receiving tVNS stimulation had a significantly higher throughput capacity than the sham group. In fact, the tVNS group’s throughput capacity decreased only 5% from their baseline at 1600 (when they first arrived at the lab, 9 hours awake) whereas the sham group’s capacity fell 15%. Twelve total minutes of non-invasive stimulation delivered at 1900 hours appears to be providing a long-lasting benefit to multi-tasking performance, 15 hours post-stimulation, when performance should be at its worst.
Given the results from the AF-MATB task that indicates the greatest performance benefit is found for tasks requiring visual attention, it is not surprising that a performance benefits for the visually-based psychomotor vigilance task (PVT) was also detected. The PVT is a simple reaction time test that requires visual attention, rapid detection and response, and more generally, measures physiological arousal levels. The results indicated that the tVNS group performed significantly better than sham on the PVT for the duration of the testing, which by the end of the study was 19 hours after stimulation. Previous research with tDCS and sleep deprivation repeatedly found that tDCS enhanced arousal levels (as measured by the PVT) compared to caffeine and sham stimulation for as long as 24-hours post stimulation. Furthermore, when the investigators delivered cervical tVNS on four consecutive days using the same device and stimulation procedures from this study, the investigators found elevated PVT accuracy scores as long as 90 days post-stimulation.
Another interesting finding from this study was the smaller increase in subjective fatigue rating by participants who received tVNS when compared to sham. It is possible, if not likely, that this reduction in fatigue is caused by activation of the LC. This brain region is involved with attention, memory, wakefulness, and arousal. These are all aspects of behavioral that showed to be influenced by tVNS. Future research should investigate other forms of cognitive enhancements and consider biomarker or imaging analysis to more deeply explore the mechanisms of action, determine why low-current neural stimulation seems to be effective, and what neural sites and regions are being differentially activated.
|Mission||Launch/Start Date||Landing/End Date||Duration|