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.

Intensity-Dependent Changes in Quantified Resting Cerebral Perfusion With Multiple Sessions of Transcranial DC Stimulation.

Transcranial direct current stimulation (tDCS) to the left prefrontal cortex has been shown to produce broad behavioral effects including enhanced learning and vigilance. Still, the neural mechanisms underlying such effects are not fully understood. Furthermore, the neural underpinnings of repeated stimulation remain understudied. In this work, we evaluated the effects of the repetition and intensity of tDCS on cerebral perfusion [cerebral blood flow (CBF)]. A cohort of 47 subjects was randomly assigned to one of the three groups. tDCS of 1- or 2-mA was applied to the left prefrontal cortex on three consecutive days, and resting CBF was quantified before and after stimulation using the arterial spin labeling MRI and then compared with a group that received sham stimulation. A widespread decreased CBF was found in a group receiving sham stimulation across the three post-stimulation measures when compared with baseline. In contrast, only slight decreases were observed in the group receiving 2-mA stimulation in the second and third post-stimulation measurements, but more prominent increased CBF was observed across several brain regions including the locus coeruleus (LC). The LC is an integral region in the production of norepinephrine and the noradrenergic system, and an increased norepinephrine/noradrenergic activity could explain the various behavioral findings from the anodal prefrontal tDCS. A decreased CBF was observed in the 1-mA group across the first two post-stimulation measurements, similar to the sham group. This decreased CBF was apparent in only a few small clusters in the third post-stimulation scan but was accompanied by an increased CBF, indicating that the neural effects of stimulation may persist for at least 24 h and that the repeated stimulation may produce cumulative effects.

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.

Transcranial Direct Current Stimulation Optimization - From Physics-Based Computer Simulations to High-Fidelity Head Phantom Fabrication and Measurements.

BACKGROUND: Transcranial direct current stimulation (tDCS) modulates neural networks. Computer simulations, while used to identify how currents behave within tissues of different conductivity properties, still need to be complemented by physical models. OBJECTIVE/HYPOTHESIS: To better understand tDCS effects on biology-mimicking tissues by developing and testing the feasibility of a high-fidelity 3D head phantom model that has sensing capabilities at different compartmental levels. METHODS: Models obtained from MRI images generated 3D printed molds. Agar phantoms were fabricated, and 18 monitoring electrodes were placed on specific phantom brain areas. RESULTS: When using rectangular electrodes, the measured and simulated voltages at the monitoring electrodes agreed reasonably well, except at excitation locations. The electric field distribution in different phantom layers appeared better confined with circular electrodes compared to rectangular electrodes. CONCLUSION: The high-fidelity 3D head model was found to be feasible and comparable with computer-based electrical simulations, with high correlation between simulated and measured brain voltages. This feasibility study supports testing to further assess the reliability of this model.

Repetitive Transcranial Electrical Stimulation Induces Quantified Changes in Resting Cerebral Perfusion Measured from Arterial Spin Labeling.

The use of transcranial electrical stimulation (TES) as a method to augment neural activity has increased in popularity in the last decade and a half. The specific application of TES to the left prefrontal cortex has been shown to produce broad cognitive effects; however, the neural mechanisms underlying these effects remain unknown. In this work, we evaluated the effect of repetitive TES on cerebral perfusion. Stimulation was applied to the left prefrontal cortex on three consecutive days, and resting cerebral perfusion was quantified before and after stimulation using arterial spin labeling. Perfusion was found to decrease significantly more in a matched sham stimulation group than in a group receiving active stimulation across many areas of the brain. These changes were found to originate in the locus coeruleus and were broadly distributed in the neocortex. The changes in the neocortex may be a direct result of the stimulation or an indirect result via the changes in the noradrenergic system produced from the altered activity of the locus coeruleus. These findings indicate that anodal left prefrontal stimulation alters the activity of the locus coeruleus, and this altered activity may excite the noradrenergic system producing the broad behavioral effects that have been reported.

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.

Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats.

A commonly referenced transcranial Direct Current Stimulation (tDCS) safety threshold derives from tDCS lesion studies in the rat and relies on electrode current density (and related electrode charge density) to support clinical guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion threshold injury (e.g. neuroinflammatory processes), and role of electrode montage across rodent and human studies support further investigation into animal models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between 0 and 5mA for 60min through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1 immunohistochemistry, and computational brain current density modeling. Brain lesion occurred after anodal tDCS at and above 0.5mA using a 25.0mm2 electrode (electrode current density: 20.0A/m2). Lesion initially occurred using smaller 10.6mm2 or 5.3mm2 electrodes at 0.25mA (23.5A/m2) and 0.5mA (94.2A/m2), respectively. Histological damage was correlated with computational brain current density predictions. Changes in microglial phenotype occurred in higher stimulation groups. Lesions were observed using anodal tDCS at an electrode current density of 20.0A/m2, which is below the previously reported safety threshold of 142.9A/m2 using cathodal tDCS. The lesion area is not simply predicted by electrode current density (and so not by charge density as duration was fixed); rather computational modeling suggests average brain current density as a better predictor for anodal tDCS. Nonetheless, under the assumption that rodent epicranial stimulation is a hypersensitive model, an electrode current density of 20.0A/m2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2A/m2 when electrodes are placed on the skin (resulting in a lower brain current density).

Transcranial direct current stimulation facilitates cognitive multi-task performance differentially depending on anode location and subtask.

There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation-specifically transcranial Direct Current Stimulation (tDCS)-has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to right and left hemispheres on subtask performance during the first 45 min of training. The strongest effects both overall and for ship flying (control and velocity subtasks) were seen with a right parietal (C4, reference to left shoulder) montage, shown by modeling to induce an electric field that includes nodes in both dorsal and ventral attention networks. This is consistent with the re-orienting hypothesis that the ventral attention network is activated along with the dorsal attention network if a new, task-relevant event occurs while visuospatial attention is focused (Corbetta et al., 2008). No effects were seen with anodes over sites that stimulated only dorsal (C3) or only ventral (F10) attention networks. The speed subtask (update memory for symbols) benefited from an F9 anode over left prefrontal cortex. These results argue for development of tDCS as a training aid in real world settings where multi-tasking is critical.

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.

Enhancing vigilance in operators with prefrontal cortex transcranial direct current stimulation (tDCS).

Sustained attention, often referred to as vigilance in humans, is the ability to maintain goal-directed behavior for extended periods of time and respond to intermittent targets in the environment. With greater time-on-task the ability to detect targets decreases and reaction time increases-a phenomenon termed the vigilance decrement. The purpose of this study was to examine the role of dorsolateral prefrontal cortex in the vigilance decrement. Subjects (n=19) received prefrontal transcranial direct current stimulation (tDCS) at one of two different time points during a vigilance task (early or late). The impact of tDCS was examined using measures of behavior, hemispheric blood flow velocity, and regional blood oxygenation relative to sham stimulation. In the sham condition greater time-on-task was accompanied by fewer target detections and slower reaction times, indicating a vigilance decrement, and decreased blood flow velocity. tDCS significantly altered baseline task-induced physiologic and behavioral changes, dependent on the time of stimulation administration and electrode configuration (determining polarity of stimulation). Compared to the sham condition, with more time-on-task blood flow velocity decreased less and cerebral oxygenation increased more in the tDCS condition. Behavioral measures showed a significant improvement in target detection performance with tDCS compared to the sham stimulation. Signal detection analysis revealed a significant change in operator discriminability and response bias with increased time-on-task, as well as interactions between time of stimulation administration and electrode configuration. Current density modeling of tDCS showed high densities in the medial prefrontal cortex and anterior cingulate cortex. These findings confirm that cerebral hemodynamic measures provide an index of resource utilization and point to the central role of the frontal cortex in vigilance. Further, they suggest that modulation of the frontal cortices-and connected structures-influences the availability of vigilance resources. These findings indicate that tDCS may be well-suited to mitigate performance degradation in work settings requiring sustained attention or as a possible treatment for neurological or psychiatric disorders involving sustained attention.

Acceleration of image analyst training with transcranial direct current stimulation.

Humans today are routinely and increasingly presented with vast quantities of data that challenge their capacity for efficient processing. To restore the balance between man and machine, it is worthwhile to explore new methods for enhancing or accelerating this capacity. This study was designed to investigate the efficacy of transcranial DC stimulation (tDCS) to reduce training time and increase proficiency in spatial recognition using a simulated synthetic aperture radar (SAR) task. Twenty-seven Air Force active duty members volunteered to participate in the study. Each participant was assigned to 1 of 3 stimulation groups and received two, 90-min training sessions on a target search and identification task using SAR imagery followed by a test. The tDCS anode was applied to site F10 according to the 10-20 electroencephalographic electrode convention while the cathode was placed on the contralateral bicep. Group 1 received anodal tDCS at 2 mA for 30 min in the first training session and sham tDCS in the second session. Group 2 received the stimulation conditions in the opposite order. Group 3 did not receive stimulation at all. Results showed that participants receiving training plus tDCS attained visual search accuracies ~25% higher than those provided with sham stimulation or no stimulation. However, a corresponding performance improvement was not found in the first training session for the change detection portion of the task. This indicates that experience with the imagery is important in the tDCS-elicited performance improvements in change detection.

Modulating the brain at work using noninvasive transcranial stimulation.

This paper proposes a shift in the way researchers currently view and use transcranial brain stimulation technologies. From a neuroscience perspective, the standard application of both transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) has been mainly to explore the function of various brain regions. These tools allow for noninvasive and painless modulation of cortical tissue. In the course of studying the function of an area, many studies often report enhanced performance of a task during or following the stimulation. However, little follow-up research is typically done to further explore these effects. Approaching this growing pool of cognitive neuroscience literature with a neuroergonomics mindset (i.e., studying the brain at work), the possibilities of using these stimulation techniques for more than simply investigating the function of cortical areas become evident. In this paper, we discuss how cognitive neuroscience brain stimulation studies may complement neuroergonomics research on human performance optimization. And, through this discussion, we hope to shift the mindset of viewing transcranial stimulation techniques as solely investigatory basic science tools or possible clinical therapeutic devices to viewing transcranial stimulation techniques as interventional tools to be incorporated in applied science research and systems for the augmentation and enhancement of human operator performance.

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.