Vagus nerve stimulation: mechanisms and factors involved in memory enhancement.

Vagus nerve stimulation (VNS) has been recognized as a useful neuromodulation tool to target the central nervous system by electrical stimulation of peripheral nerves. Activation of the nucleus of the solitary tract (NTS) in the brainstem by vagal afferent nerve fibers allows for modulation of various higher order brain regions, including limbic and cerebral cortex structures. Along with neurological and psychiatric indications, clinical and preclinical studies suggest that VNS can improve memory. While the underlying mechanisms to improve memory with VNS involve brain areas, such as the prefrontal cortex and processes including alertness and arousal, here we focus on VNS-induced memory improvements related to the hippocampus, the main area implicated in memory acquisition. In addition, we detail research demonstrating that a targeted approach to VNS can modify memory outcomes and delve into the molecular mechanisms associated with these changes. These findings indicate that a greater understanding of VNS mechanisms while also considering stimulation parameters, administration site, timing in relation to training, and sex-specific factors, may allow for optimal VNS application to enhance memory.

Transcranial Direct Current Stimulation Modulates Connectivity of Left Dorsolateral Prefrontal Cortex with Distributed Cortical Networks.

Studies have shown that transcranial direct current stimulation increases neuronal excitability of the targeted region and general connectivity of relevant functional networks. However, relatively little is understood of how the stimulation affects the connectivity relationship of the target with regions across the network structure of the brain. Here, we investigated the effects of transcranial direct current stimulation on the functional connectivity of the targeted region using resting-state fMRI scans of the human brain. Anodal direct current stimulation was applied to the left dorsolateral prefrontal cortex (lDLPFC; cathode on the right bicep), which belongs to the frontoparietal control network (FPCN) and is commonly targeted for neuromodulation of various cognitive functions including short-term memory, long-term memory, and cognitive control. lDLPFC's connectivity characteristics were quantified as graph theory measures, from the resting-state fMRI scans obtained prior to and following the stimulation. Critically, we tested pre- to poststimulation changes of the lDLPFC connectivity metrics following an active versus sham stimulation. We found that the stimulation had two distinct effects on the connectivity of lDLPFC: for Brodmann's area (BA) 9, it increased the functional connectivity between BA 9 and other nodes within the FPCN; for BA 46, net connectivity strength was not altered within FPCN, but connectivity distribution across networks (participation coefficient) was decreased. These findings provide insights that the behavioral changes as the functional consequences of stimulation may come about because of the increased role of lDLPFC in the FPCN.

Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress.

Fatigue is a pervasive public health and safety issue. Common fatigue countermeasures include caffeine or other chemical stimulants. These can be effective in limited circumstances but other non-pharmacological fatigue countermeasures such as non-invasive electrical neuromodulation have shown promise. It is reasonable to suspect that other types of non-invasive neuromodulation may be similarly effective or perhaps even superior. The objective of this research was to evaluate the efficacy of cervical transcutaneous vagal nerve stimulation (ctVNS) to mitigate the negative effects of fatigue on cognition and mood. Two groups (active or sham stimulation) of twenty participants in each group completed 34 h of sustained wakefulness. The ctVNS group performed significantly better on arousal, multi-tasking, and reported significantly lower fatigue ratings compared to sham for the duration of the study. CtVNS could be a powerful fatigue countermeasure tool that is easy to administer, long-lasting, and has fewer side-effects compared to common pharmacological interventions.

The Effects of Anodal Transcranial Direct Current Stimulation on Sleep Time and Efficiency.

A single session of anodal transcranial direct current stimulation (tDCS) has been shown to increase arousal in healthy participants for up to 24 h post-stimulation. However, little is known about the effects of tDCS on subsequent sleep in this population. Based on previous clinical studies, we hypothesized that anodal stimulation to the left dorsolateral prefrontal cortex (lDLPFC) would produce higher arousal with decreased sleep time and stimulation to the primary motor cortex (M1) would have the converse effect. Thirty-six active duty military were randomized into one of three groups (n = 12/group); active anodal tDCS over the lDLPFC, active anodal tDCS over left M1, or sham tDCS. Participants answered questionnaires 3 times a day and wore a wrist activity monitor (WAM) to measure sleep time and efficiency for 3 weeks. On weeks 2 and 3 (order counterbalance), participants received stimulation at 1800 h before 26 h of sustained wakefulness testing (sleep deprived) and at 1800 h without sleep deprivation (non-sleep deprived). There were no significant effects for the non-sleep deprived portion of testing. For the sleep deprived portion of testing, there were main effects of group and night on sleep time. The DLPFC group slept less than the other groups on the second and third night following stimulation. There is no negative effect on mood or sleep quality from a single dose of tDCS when participants have normal sleep patterns (i.e., non-sleep deprived portion of testing). The results suggest that stimulation may result in faster recovery from fatigue caused by acute periods of sleep deprivation, as their recovery sleep periods were less.

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships in Healthy Humans.

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects-primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation. Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices. Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS.

Transcranial direct current stimulation versus caffeine as a fatigue countermeasure.

BACKGROUND: To assess the efficacy of using transcranial direct current stimulation (tDCS) to remediate the deleterious effects of fatigue induced by sleep deprivation and compare these results to caffeine, a commonly used fatigue countermeasure. OBJECTIVE/HYPOTHESIS: Based on previous research, tDCS of the dorsolateral prefrontal cortex (DLPFC) can modulate attention and arousal. The authors hypothesize that tDCS can be an effective fatigue countermeasure. METHODS: Five groups of ten participants each received either active tDCS and placebo gum at 1800, caffeine gum with sham tDCS at 1800, active tDCS and placebo gum at 0400, caffeine gum with sham tDCS at 0400, or sham tDCS with placebo gum at 1800 and 0400 during 36-h of sustained wakefulness. Participants completed a vigilance task, working memory task, psychomotor vigilance task (PVT), and a procedural game beginning at 1800 h and continued every two hours throughout the night until 1900 the next day. RESULTS: tDCS dosed at 1800 provided 6 h of improved attentional accuracy and reaction times compared to the control group. Caffeine did not produce an effect. Both tDCS groups also had an improved effect on mood. Participants receiving tDCS reported feeling more vigor, less fatigue, and less bored throughout the night compared to the control and caffeine groups. CONCLUSIONS: We believe tDCS could be a powerful fatigue countermeasure. The effects appear to be comparable or possibly more beneficial than caffeine because they are longer lasting and mood remains more positive.

Individual differences in biophysiological toughness: sustaining working memory during physical exhaustion.

Recent evidence suggests that increased dehydroepiandrosterone sulfate (DHEAS), in combination with decreased cortisol levels have been correlated with enhanced performance outcomes in stressful military environments. This study was implemented to replicate these findings in a group of active duty Air Force members to provide information on the usefulness of these biomarkers indices in the training and operational environment. Seventeen active duty males participated in the 4 sessions of this study. Sessions 1 and 2 were training days for the cognitive testing. Session 3 was a baseline measure of physical fitness, utilizing the VO2 Maximal Treadmill test. Session 4 was centered around a modified-Astrand treadmill protocol designed to induce physical exhaustion. Blood draws for biomarker analysis, cognitive testing (NovaScan), psychomotor vigilance, and physiological measures were collected before, during, and following the treadmill protocol. Results showed that prolonged increases in cortisol negatively correlate with working memory performance. DHEAS release from baseline to poststress was negatively related to the changes in cortisol for 20 minutes following stress. These results indicate that the ratio of DHEAS to cortisol buffers, the effect of cortisol increases that are related to poor working memory performance because of physical exhaustion.

A comparison of the effects of transcranial direct current stimulation and caffeine on vigilance and cognitive performance during extended wakefulness.

BACKGROUND: Sleep deprivation from extended duty hours is a common complaint for many occupations. Caffeine is one of the most common countermeasures used to combat fatigue. However, the benefits of caffeine decline over time and with chronic use. OBJECTIVE: Our objective was to evaluate the efficacy of anodal transcranial direct current stimulation (tDCS) applied to the pre-frontal cortex at 2 mA for 30 min to remediate the effects of sleep deprivation and to compare the behavioral effects of tDCS with those of caffeine. METHODS: Three groups of 10 participants each received either active tDCS with placebo gum, caffeine gum with sham tDCS, or sham tDCS with placebo gum during 30 h of extended wakefulness. RESULTS: Our results show that tDCS prevented a decrement in vigilance and led to better subjective ratings for fatigue, drowsiness, energy, and composite mood compared to caffeine and control in sleep-deprived individuals. Both the tDCS and caffeine produced similar improvements in latencies on a short-term memory task and faster reaction times in a psychomotor task when compared to the placebo group. Interestingly, changes in accuracy for the tDCS group were not correlated to changes in mood; whereas, there was a relationship for the caffeine and sham groups. CONCLUSION: Our data suggest that tDCS could be a useful fatigue countermeasure and may be more beneficial than caffeine since boosts in performance and mood last several hours.

Detection of vigilance performance using eye blinks.

Research has shown that sustained attention or vigilance declines over time on task. Sustained attention is necessary in many environments such as air traffic controllers, cyber operators, and imagery analysts. A lapse of attention in any one of these environments can have harmful consequences. The purpose of this study was to determine if eye blink metrics from an eye-tracker are related to changes in vigilance performance and cerebral blood flow velocities. Nineteen participants performed a vigilance task while wearing an eye-tracker on four separate days. Blink frequency and duration changed significantly over time during the task. Both blink frequency and duration increased as performance declined and right cerebral blood flow velocity declined. These results suggest that eye blink information may be an indicator of arousal levels. Using an eye-tracker to detect changes in eye blinks in an operational environment would allow preventative measures to be implemented, perhaps by providing perceptual warning signals or augmenting human cognition through non-invasive brain stimulation techniques.

Evaluation of eye metrics as a detector of fatigue.

OBJECTIVES: This study evaluated oculometrics as a detector of fatigue in Air Force-relevant tasks after sleep deprivation. Using the metrics of total eye closure duration (PERCLOS) and approximate entropy (ApEn), the relation between these eye metrics and fatigue-induced performance decrements was investigated. BACKGROUND: One damaging effect to the successful outcome of operational military missions is that attributed to sleep deprivation-induced fatigue. Consequently, there is interest in the development of reliable monitoring devices that can assess when an operator is overly fatigued. METHOD: Ten civilian participants volunteered to serve in this study. Each was trained on three performance tasks: target identification, unmanned aerial vehicle landing, and the psychomotor vigilance task (PVT). Experimental testing began after 14 hr awake and continued every 2 hr until 28 hr of sleep deprivation was reached. RESULTS: Performance on the PVT and target identification tasks declined significantly as the level of sleep deprivation increased.These performance declines were paralleled more closely by changes in the ApEn compared to the PERCLOS measure. CONCLUSION: The results provide evidence that the ApEn eye metric can be used to detect fatigue in relevant military aviation tasks. APPLICATION: Military and commercial operators could benefit from an alertness monitoring device.

Operator selection for unmanned aerial systems: comparing video game players and pilots.

INTRODUCTION: Popular unmanned aerial system (UAS) platforms such as the MQ-1 Predator and MQ-9 Reaper have experienced accelerated operations tempos that have outpaced current operator training regimens, leading to a shortage of qualified UAS operators. To find a surrogate to replace pilots of manned aircraft as UAS operators, this study evaluated video game players (VGPs), pilots, and a control group on a set of UAS operation relevant cognitive tasks. METHODS: There were 30 participants who volunteered for this study and were divided into 3 groups: experienced pilots (P), experienced VGPs, and a control group (C). Each was trained on eight cognitive performance tasks relevant to unmanned flight tasks. RESULTS: The results indicated that pilots significantly outperform the VGP and control groups on multi-attribute cognitive tasks (Tank mean: VGP = 465 +/- 1.046 vs. P = 203 +/- 0.237 vs. C = 351 +/- 0.601). However, the VGPs outperformed pilots on cognitive tests related to visually acquiring, identifying, and tracking targets (final score: VGP = 594.28 +/- 8.708 vs. P = 563.33 +/- 8.787 vs. C = 568.21 +/- 8.224). Likewise, both VGPs and pilots performed similarly on the UAS landing task, but outperformed the control group (glide slope: VGP = 40.982 +/- 3.244 vs. P = 30.461 +/- 2.251 vs. C = 57.060 +/- 4.407). CONCLUSIONS: Cognitive skills learned in video game play may transfer to novel environments and improve performance in UAS tasks over individuals with no video game experience.