Evaluating the efficacy of cranial electrotherapy stimulation in mitigating anxiety-induced cognitive deficits.

Cranial electrotherapy stimulation (CES) is a form of non-invasive brain stimulation (NIBS) that has demonstrated potential to modulate neural activity in a manner that may be conducive to improved cognitive performance. While other forms of NIBS, such as transcranial direct current stimulation (tDCS), have received attention in the field as potential acute cognitive enhancers, CES remains relatively unexplored. The current study aimed to assess the efficacy of CES in improving acute cognitive performance under normal experimental conditions, as well as during sessions of induced situational anxiety (threat of shock or ToS). To study this question, participants completed a cognitive battery assessing processing speed and distinct aspects of executive functioning (working memory, inhibition, and task switching) in two separate sessions in which they received active and sham CES. Participants were randomly assigned to between subject groups of either situational anxiety (ToS) or control condition (no ToS). We predicted that active CES would improve performance on assessments of executive functioning (working memory, inhibition, and task switching) relative to sham CES under ToS. We did not find any significant effects of ToS, CES, or an interaction between ToS and CES for any measures of executive functioning or processing speed. These findings suggest that a single dose of CES does not enhance executive functioning or processing speed under normal conditions or during ToS.

Proteomic and metabolomic profiling of acute and chronic stress events associated with military exercises.

By characterizing physiological changes that occur in warfighters during simulated combat, we can start to unravel the key biomolecular components that are linked to physical and cognitive performance. Viable field-based sensors for the warfighter must be rapid and noninvasive. In an effort to facilitate this, we applied a multiomics pipeline to characterize the stress response in the saliva of warfighters to correlate biomolecular changes with overall performance and health. In this study, two different stress models were observed - one of chronic stress and one of acute stress. In both models, significant perturbations in the immune, metabolic, and protein manufacturing/processing systems were observed. However, when differentiating between stress models, specific metabolites associated with the "fight or flight" response and protein folding were seen to be discriminate of the acute stress model.

Building a transdisciplinary expert consensus on the cognitive drivers of performance under pressure: An international multi-panel Delphi study.

Introduction: The ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport. Despite recognition that such performance depends on a range of cognitive factors, how common these factors are across performance domains remains unclear. The current study sought to integrate existing knowledge in the performance field in the form of a transdisciplinary expert consensus on the cognitive mechanisms that underlie performance under pressure. Methods: International experts were recruited from four performance domains [(i) Defense; (ii) Competitive Sport; (iii) Civilian High-stakes; and (iv) Performance Neuroscience]. Experts rated constructs from the Research Domain Criteria (RDoC) framework (and several expert-suggested constructs) across successive rounds, until all constructs reached consensus for inclusion or were eliminated. Finally, included constructs were ranked for their relative importance. Results: Sixty-eight experts completed the first Delphi round, with 94% of experts retained by the end of the Delphi process. The following 10 constructs reached consensus across all four panels (in order of overall ranking): (1) Attention; (2) Cognitive Control-Performance Monitoring; (3) Arousal and Regulatory Systems-Arousal; (4) Cognitive Control-Goal Selection, Updating, Representation, and Maintenance; (5) Cognitive Control-Response Selection and Inhibition/Suppression; (6) Working memory-Flexible Updating; (7) Working memory-Active Maintenance; (8) Perception and Understanding of Self-Self-knowledge; (9) Working memory-Interference Control, and (10) Expert-suggested-Shifting. Discussion: Our results identify a set of transdisciplinary neuroscience-informed constructs, validated through expert consensus. This expert consensus is critical to standardizing cognitive assessment and informing mechanism-targeted interventions in the broader field of human performance optimization.

A Critical Review of Cranial Electrotherapy Stimulation for Neuromodulation in Clinical and Non-clinical Samples.

Cranial electrotherapy stimulation (CES) is a neuromodulation tool used for treating several clinical disorders, including insomnia, anxiety, and depression. More recently, a limited number of studies have examined CES for altering affect, physiology, and behavior in healthy, non-clinical samples. The physiological, neurochemical, and metabolic mechanisms underlying CES effects are currently unknown. Computational modeling suggests that electrical current administered with CES at the earlobes can reach cortical and subcortical regions at very low intensities associated with subthreshold neuromodulatory effects, and studies using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) show some effects on alpha band EEG activity, and modulation of the default mode network during CES administration. One theory suggests that CES modulates brain stem (e.g., medulla), limbic (e.g., thalamus, amygdala), and cortical (e.g., prefrontal cortex) regions and increases relative parasympathetic to sympathetic drive in the autonomic nervous system. There is no direct evidence supporting this theory, but one of its assumptions is that CES may induce its effects by stimulating afferent projections of the vagus nerve, which provides parasympathetic signals to the cardiorespiratory and digestive systems. In our critical review of studies using CES in clinical and non-clinical populations, we found severe methodological concerns, including potential conflicts of interest, risk of methodological and analytic biases, issues with sham credibility, lack of blinding, and a severe heterogeneity of CES parameters selected and employed across scientists, laboratories, institutions, and studies. These limitations make it difficult to derive consistent or compelling insights from the extant literature, tempering enthusiasm for CES and its potential to alter nervous system activity or behavior in meaningful or reliable ways. The lack of compelling evidence also motivates well-designed and relatively high-powered experiments to assess how CES might modulate the physiological, affective, and cognitive responses to stress. Establishing reliable empirical links between CES administration and human performance is critical for supporting its prospective use during occupational training, operations, or recovery, ensuring reliability and robustness of effects, characterizing if, when, and in whom such effects might arise, and ensuring that any benefits of CES outweigh the risks of adverse events.

The Specificity of Cognitive-Motor Dual-Task Interference on Balance in Young and Older Adults.

Standing upright on stable and unstable surfaces requires postural control. Postural control declines as humans age, presenting greater risk of fall-related injury and other negative health outcomes. Secondary cognitive tasks can further impact balance, which highlights the importance of coordination between cognitive and motor processes. Past research indicates that this coordination relies on executive function (EF; the ability to control, maintain, and flexibly direct attention to achieve goals), which coincidentally declines as humans age. This suggests that secondary cognitive tasks requiring EF may exert a greater influence on balance compared to non-EF secondary tasks, and this interaction could be exaggerated among older adults. In the current study, we had younger and older adults complete two Surface Stability conditions (standing upright on stable vs. unstable surfaces) under varying Cognitive Load; participants completed EF (Shifting, Inhibiting, Updating) and non-EF (Processing Speed) secondary cognitive tasks on tablets, as well as a single task control scenario with no secondary cognitive task. Our primary balance measure of interest was sway area, which was measured with an array of wearable inertial measurement unit sensors. Replicating prior work, we found a main effect of Surface Stability with less sway on stable surfaces compared to unstable surfaces, and we found an interaction between Age and Surface Stability with older adults exhibiting significantly greater sway selectively on unstable surfaces compared to younger adults. New findings revealed a main effect of Cognitive Load on sway, with the single task condition having significantly less sway than two of the EF conditions (Updating and Shifting) and the non-EF condition (Processing Speed). We also found an interaction of Cognitive Load and Surface Stability on postural control, where Surface Stability impacted sway the most for the single task and two of the executive function conditions (Inhibition and Shifting). Interestingly, Age did not interact with Cognitive Load, suggesting that both age groups were equally impacted by secondary cognitive tasks, regardless the presence or type of secondary cognitive task. Taken together, these patterns suggest that cognitive demands vary in their impact on posture control across stable vs. unstable surfaces, and that EF involvement may not be the driving mechanism explaining cognitive-motor dual-task interference on balance.

Effects of Cognitive Over Postural Demands on Upright Standing Among Young Adults.

A growing body of research has shown that static stance control (e.g., body sway) is influenced by cognitive demands (CD), an effect that may be related to competition for limited central resources. Measures of stance control have also been impacted by postural demands (PD) (e.g., stable vs. unstable stances). However, less is known of any possible interactions between PD and CD on static stance control in populations with intact balance control and ample cognitive resources, like young healthy adults. In this study, among the same participants, we factorially compared the impact of PD with and without CD on static stance control. Thirty-four healthy young adults wore inertial measurement units (IMU) while completing static stance tasks for 30 seconds in three different PD positions: feet apart, feet together, and tandem feet. After completing these tasks alone, participants performed these tasks with CD by concurrently completing verbal serial seven subtractions from a randomly selected three-digit number. For two dependent measures, path length and jerk, there were main effects of CD and PD but no interaction effect between these factors. For all other stance control parameters, there was only a PD main effect. Thus, adding a cognitive demand to postural demands, while standing upright, may have an independent impact on stance control, but CD does not seem to interact with PD. These results suggest that young healthy adults may be less sensitive to simple PD and CD due to their greater inherent balance control and available cognitive resources. Future work might explore more complex PD and CD combinations to determine the boundaries under which young adults' resources are taxed.

Combined and Isolated Effects of Acute Exercise and Brain Stimulation on Executive Function in Healthy Young Adults.

Abstract: Acute cognitive enhancement has been sought by healthy young individuals to improve academic and professional performance. Among several methods, physical exercise interventions and transcranial direct current brain stimulation (tDCS) have shown promise in impacting executive functions. Here, we observed a set of new findings about the causal effect of acute aerobic exercise and tDCS across three facets of executive function: Inhibition (as measured by a flanker task) was selectively impacted by acute aerobic exercise but not tDCS, whereas working memory (as measured by an n-back task) was impacted by both acute aerobic exercise and tDCS, with effects emerging on distinct processing components for each manipulation. Sustained attention (as measured by the Mackworth clock task), on the other hand, was not impacted by acute aerobic exercise or tDCS. Interestingly, no effects of combining acute aerobic exercise and tDCS emerged. We argue that understanding the unique and combined contributions of these cognitive enhancement techniques can not only contribute to a deeper mechanistic explanation in healthy individuals but also inform future research with clinical and aging populations.

Building the multitasking brain: An integrated perspective on functional brain activation during task-switching and dual-tasking.

Multitasking behavior is associated with well-known performance costs, but the question of why individuals falter when attempting to manage multiple streams of information remains difficult to answer. One reason for this difficulty may be that multitasking costs are often characterized by isolating component processes that are studied largely independently. In this study, we instead integrate two commonly studied substrates of multitasking, task-switching and dual-tasking, within the same procedural context. This method allows not only a direct comparison of performance costs associated with different demand types but also examination of their interaction. We measured functional brain activation in thirty healthy young adults as they completed a block-design version of the task, observing consistent and separable patterns of frontoparietal activation as a function of demand type. Broadly, task-switching was associated with activation of left premotor and inferior parietal regions, and dual-tasking was associated with activation in regions of right prefrontal and inferior parietal cortex. In the interaction condition, we observed a distributed bilateral pattern of activation across the areas associated with each demand in isolation. These results provide both behavioral and neuroimaging evidence that task-switching and dual-tasking demands can be dissociated and contribute to multitasking costs in unique and separable ways.

Modulating Applied Task Performance via Transcranial Electrical Stimulation.

Basic and applied research are increasingly adopting transcranial electrical stimulation (tES) for modulating perceptual, cognitive, affective, and motor processes. Industry and defense applications of tES hold potential for accelerating training and knowledge acquisition and sustaining work-related performance in the face of fatigue, workload, and stress. This mini-review article describes the promises and perils of tES, and reviews research testing its influence on two broad applied areas: sustaining and dividing attention, and operating in virtual environments. Also included is a discussion of challenges related to viable mechanistic explanations for tES effectiveness, attempts at replication and consideration of null results, and the potential importance of individual differences in predicting tES influences on human performance. Finally, future research directions are proposed to address these challenges and help develop a fuller understanding of tES viability for enhancing real-world performance.

Rapid liquid chromatography tandem mass spectrometry method for targeted quantitation of human performance metabolites in saliva.

Saliva is increasingly being targeted for metabolic studies due to its non-invasive collection methods. Tracing levels of certain metabolites within biofluids can provide indications for a myriad of physiological conditions. This study was performed on a panel of eight analytes found in saliva that have shown associations with physiological conditions of human performance, such as stress, inflammation, and circadian rhythm. This dual polarity liquid chromatography tandem mass spectrometric (LCMS/MS) method was developed to accommodate a diverse group of analytes including steroids, alkaloids, and neurotransmitters. Samples collected during field exercises from soldiers were compared to those of civilians and baseline levels of each of these compounds was determined in saliva. Although most analytes showed no significant differences between the two populations, relative cortisol levels were higher for soldiers than for civilians. This developed dual polarity LCMS/MS method can be applied to very diverse groups of salivary analytes simultaneously.

Single neuron recordings of bilinguals performing in a continuous recognition memory task.

We report the results of a bilingual continuous recognition memory task during which single- and multi-neuron activity was recorded in human subjects with intracranial microwire implants. Subjects (n = 5) were right-handed Spanish-English bilinguals who were undergoing evaluation prior to surgery for severe epilepsy. Subjects were presented with Spanish and English words and the task was to determine whether any given word had been seen earlier in the testing session, irrespective of the language in which it had appeared. Recordings in the left and right hippocampus revealed notable laterality, whereby both Spanish and English items that had been seen previously in the other language (switch trials) triggered increased neural firing in the left hippocampus. Items that had been seen previously in the same language (repeat trials) triggered increased neural firings in the right hippocampus. These results are consistent with theories that propose roles of both the left- and right-hemisphere in real-time linguistic processing. Importantly, this experiment presents the first instance of intracranial recordings in bilinguals performing a task with switching demands.

Why reread? Evidence from garden-path and local coherence structures.

Two eye-tracking experiments were conducted to compare the online reading and offline comprehension of main verb/reduced relative garden-path sentences and local coherence sentences. Rereading of early material in garden-path reduced relatives should be revisionary, aimed at reanalysing an earlier misparse; however, rereading of early material in a local coherence reduced relative need only be confirmatory, as the original parse of the earlier portion of these sentences is ultimately correct. Results of online and offline measures showed that local coherence structures elicited signals of reading disruption that arose earlier and lasted longer, and local coherence comprehension was also better than garden path comprehension. Few rereading measures in either sentence type were predicted by structural features of these sentences, nor was rereading related to comprehension accuracy, which was extremely low overall. Results are discussed with respect to selective reanalysis and good-enough processing.

Memory and language improvements following cognitive control training.

Cognitive control refers to adjusting thoughts and actions when confronted with conflict during information processing. We tested whether this ability is causally linked to performance on certain language and memory tasks by using cognitive control training to systematically modulate people's ability to resolve information-conflict across domains. Different groups of subjects trained on 1 of 3 minimally different versions of an n-back task: n-back-with-lures (High-Conflict), n-back-without-lures (Low-Conflict), or 3-back-without-lures (3-Back). Subjects completed a battery of recognition memory and language processing tasks that comprised both high- and low-conflict conditions before and after training. We compared the transfer profiles of (a) the High- versus Low-Conflict groups to test how conflict resolution training contributes to transfer effects, and (b) the 3-Back versus Low-Conflict groups to test for differences not involving cognitive control. High-Conflict training-but not Low-Conflict training-produced discernable benefits on several untrained transfer tasks, but only under selective conditions requiring cognitive control. This suggests that the conflict-focused intervention influenced functioning on ostensibly different outcome measures across memory and language domains. 3-Back training resulted in occasional improvements on the outcome measures, but these were not selective for conditions involving conflict resolution. We conclude that domain-general cognitive control mechanisms are plastic, at least temporarily, and may play a causal role in linguistic and nonlinguistic performance. (PsycINFO Database Record

Language and Memory Improvements following tDCS of Left Lateral Prefrontal Cortex.

Recent research demonstrates that performance on executive-control measures can be enhanced through brain stimulation of lateral prefrontal regions. Separate psycholinguistic work emphasizes the importance of left lateral prefrontal cortex executive-control resources during sentence processing, especially when readers must override early, incorrect interpretations when faced with temporary ambiguity. Using transcranial direct current stimulation, we tested whether stimulation of left lateral prefrontal cortex had discriminate effects on language and memory conditions that rely on executive-control (versus cases with minimal executive-control demands, even in the face of task difficulty). Participants were randomly assigned to receive Anodal, Cathodal, or Sham stimulation of left lateral prefrontal cortex while they (1) processed ambiguous and unambiguous sentences in a word-by-word self-paced reading task and (2) performed an n-back memory task that, on some trials, contained interference lure items reputed to require executive-control. Across both tasks, we parametrically manipulated executive-control demands and task difficulty. Our results revealed that the Anodal group outperformed the remaining groups on (1) the sentence processing conditions requiring executive-control, and (2) only the most complex n-back conditions, regardless of executive-control demands. Together, these findings add to the mounting evidence for the selective causal role of left lateral prefrontal cortex for executive-control tasks in the language domain. Moreover, we provide the first evidence suggesting that brain stimulation is a promising method to mitigate processing demands encountered during online sentence processing.

Retrieval dynamics in self-terminated memory search.

Most free-recall experiments employ a paradigm in which participants are given a preset amount of time to retrieve items from a list. While much has been learned using this paradigm, it ignores an important component of many real-world retrieval tasks: the decision to terminate memory search. The present study examines the temporal characteristics underlying memory search by comparing within subjects a standard retrieval paradigm with a finite, preset amount of time (closed interval) to a design that allows participants to terminate memory search on their own (open interval). Calling on the results of several presented simulations, we anticipated that the threshold for number of retrieval failures varied as a function of the nature of the recall paradigm, such that open intervals should result in lower thresholds than closed intervals. Moreover, this effect was expected to manifest in interretrieval times (IRTs). Although retrieval-interval type did not significantly impact the number of items recalled or error rates, IRTs were sensitive to the manipulation. Specifically, the final IRTs in the closed-interval paradigm were longer than those of the open-interval paradigm. This pattern suggests that providing participants with a preset retrieval interval not only masks an important component of the retrieval process (the memory search termination decision), but also alters temporal retrieval dynamics. Task demands may compel people to strategically control aspects of their retrieval by implementing different stopping rules.

The benefits of executive control training and the implications for language processing.

Recent psycholinguistics research suggests that the executive function (EF) skill known as conflict resolution - the ability to adjust behavior in the service of resolving among incompatible representations - is important for several language processing tasks such as lexical and syntactic ambiguity resolution, verbal fluency, and common-ground assessment. Here, we discuss work showing that various EF skills can be enhanced through consistent practice with working-memory tasks that tap these EFs, and, moreover, that improvements on the training tasks transfer across domains to novel tasks that may rely on shared underlying EFs. These findings have implications for language processing and could launch new research exploring if EF training, within a "process-specific" framework, could be used as a remediation tool for improving general language use. Indeed, work in our lab demonstrates that EF training that increases conflict-resolution processes has selective benefits on an untrained sentence-processing task requiring syntactic ambiguity resolution, which relies on shared conflict-resolution functions. Given claims that conflict-resolution abilities contribute to a range of linguistic skills, EF training targeting this process could theoretically yield wider performance gains beyond garden-path recovery. We offer some hypotheses on the potential benefits of EF training as a component of interventions to mitigate general difficulties in language processing. However, there are caveats to consider as well, which we also address.