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.

Our previous work demonstrates that reduced activation of the executive network is associated with slow walking speed in a cohort of older adults from the MOBILIZE Boston Study. However, the influence of underlying white matter integrity on the activation of this network and walking speed is unknown. Thus, we used diffusion-weighted imaging and fMRI during an n-back task to assess associations between executive network structure, function, and walking speed. Whole-brain tract-based spatial statistics (TBSS) were used to identify regions of white matter microstructural integrity that were associated with walking speed. The integrity of these regions was then entered into multiple regression models to predict task performance and executive network activation during the n-back task. Among the significant associations of FA with walking speed, we observed the anterior thalamic radiation and superior longitudinal fasciculus were further associated with both n-back response speed and executive network activation. These findings suggest that subtle damage to frontal white matter may contribute to altered executive network activation and slower walking in older adults.

Objective: Metabolic syndrome (MetS), the presence of three or more cardiovascular risk factors, has been associated with subtle and diffuse neural compromise but has not been consistently associated with cognitive dysfunction. Sustained attention is a fundamental cognitive operation that relies on multiple brain networks and is impaired in a broad array of neurologic conditions. We examined whether a well-validated measure of sustained attention would be sensitive to vascular risk, as compared with more standard neuropsychological measures of attention and executive functioning. Method: We assessed vascular risk factors (VRFs; blood pressure, waist circumference, cholesterol, glucose, and triglycerides) in 93 middle-to-older aged adults (45-75 years). MetS was defined based on current guidelines from the National Cholesterol Education Program Adult Training Program (NCEP ATP III). Participants were grouped according to number of VRFs: high risk (MetS; 3ϩ VRFs; N ϭ 32), medium risk (1 or 2 VRFs; N ϭ 35), and low risk (0 VRFs; N ϭ 26). All participants underwent a neuropsychological battery of tests measuring executive functioning. Participants also performed the gradual-onset continuous performance task (gradCPT), a measure of sustained attention. Results: There was a significant main effect of VRF group on sustained attention performance; participants with lower vascular risk were better able to sustain attention. No significant effects were detected on standard neuropsychological tests of executive function. Conclusion: Our results suggest that the gradCPT is sensitive to the potentially negative effects of MetS on subtle aspects of neurocognitive functioning.

Background In older adults, compromised white matter tract integrity within the brain has been linked to impairments in mobility. We contend that poorer integrity disrupts mobility by altering the processing of sensorimotor and cognitive and attentional resources in neural networks. The richness of information processing in a given network can be quantified by calculating the complexity of resting-state functional MRI time series. We hypothesized that (i) older adults with lower brain complexity, specifically within sensorimotor, executive, and attention networks, would exhibit slower walking speed and greater dual-task costs (ie, dual-task cost) and (ii) such complexity would mediate the effect of white matter integrity on these metrics of mobility. Methods Fifty-three older adults completed a walking assessment and a neuroimaging protocol. Brain complexity was quantified by calculating the multiscale entropy of the resting-state functional MRI signal within seven previously defined functional networks. The white matter integrity across structures of the corpus callosum was quantified using fractional anisotropy. Results Participants with lower resting-state complexity within the sensorimotor, executive, and attention networks walked more slowly under single- and dual-task (ie, walking while performing a serial-subtraction task) conditions (β > 0.28, p ≤ .01) and had a greater dual-task cost (β < −0.28, p < .04). Complexity in these networks mediated the influence of the corpus callosum genu on both single- (indirect effects > 0.15, 95% confidence intervals = 0.02–0.32) and dual-task walking speeds (indirect effects > 0.13, 95% confidence intervals = 0.02–0.33). Conclusion These results suggest that the multiscale dynamics of resting-state brain activity correlate with mobility and mediate the effect of the microstructural integrity in the corpus callosum genu on walking speed in older adults.