Prefrontal Multielectrode Transcranial Direct Current Stimulation Modulates Performance and Neural Activity Serving Visuospatial Processing.

The dorsolateral prefrontal cortex (DLPFC) is known to play a critical role in visuospatial attention and processing, but the relative contribution of the left versus right DLPFC remains poorly understood. We applied multielectrode transcranial direct-current stimulation (ME-tDCS) to the left and right DLPFC to investigate its net impact on behavioral performance and population-level neural activity. The primary hypothesis was that significant laterality effects would be observed in regard to behavior and neural oscillations. Twenty-five healthy adults underwent three visits (left, right, and sham ME-tDCS). Following stimulation, participants completed a visuospatial processing task during magnetoencephalography (MEG). Statistically significant oscillatory events were imaged, and time series were then extracted from the peak voxels of each response. Behavioral findings indicated differences in reaction time and accuracy, with left DLPFC stimulation being associated with slower responses and decreased accuracy compared to right stimulation. Left DLPFC stimulation was also associated with increases in spontaneous theta and decreases in gamma within occipital cortices relative to both right and sham stimulation, while connectivity among DLPFC and visual cortices was generally increased contralateral to stimulation. These data suggest spectrally specific modulation of spontaneous cortical activity at the network-level by ME-tDCS, with distinct outcomes based on the laterality of stimulation.

Multielectrode Transcranial Electrical Stimulation of the Left and Right Prefrontal Cortices Differentially Impacts Verbal Working Memory Neural Circuitry.

Recent studies have examined the effects of conventional transcranial direct current stimulation (tDCS) on working memory (WM) performance, but this method has relatively low spatial precision and generally involves a reference electrode that complicates interpretation. Herein, we report a repeated-measures crossover study of 25 healthy adults who underwent multielectrode tDCS of the left dorsolateral prefrontal cortex (DLPFC), right DLPFC, or sham in 3 separate visits. Shortly after each stimulation session, participants performed a verbal WM (VWM) task during magnetoencephalography, and the resulting data were examined in the time-frequency domain and imaged using a beamformer. We found that after left DLPFC stimulation, participants exhibited stronger responses across a network of left-lateralized cortical areas, including the supramarginal gyrus, prefrontal cortex, inferior frontal gyrus, and cuneus, as well as the right hemispheric homologues of these regions. Importantly, these effects were specific to the alpha-band, which has been previously implicated in VWM processing. Although stimulation condition did not significantly affect performance, stepwise regression revealed a relationship between reaction time and response amplitude in the left precuneus and supramarginal gyrus. These findings suggest that multielectrode tDCS targeting the left DLPFC affects the neural dynamics underlying offline VWM processing, including utilization of a more extensive bilateral cortical network.

Epigenetic Markers of Aging Predict the Neural Oscillations Serving Selective Attention.

Chronological age remains an imperfect measure of accumulated physiological stress. Biological measures of aging may provide key advantages, allowing scientists focusing on age-related functional changes to use metrics derived from epigenetic factors like DNA methylation (DNAm), which could provide greater precision. Here we investigated the relationship between methylation-based age and an essential cognitive function that is known to exhibit age-related decline: selective attention. We found that DNAm-age predicted selective attention abilities and fully mediated the relationship between selective attention and chronological age. Using neuroimaging with magnetoencephalography, we found that gamma activity in the anterior cingulate was robustly predicted by DNAm-derived biological age, revealing the neural dynamics underlying this DNAm age-related cognitive decline. Anterior cingulate gamma activity also significantly predicted behavior on the selective attention task, indicating its functional relevance. These findings suggest that DNAm age may be a better predictor of cognitive and brain aging than more traditional chronological metrics.

High-definition transcranial direct current stimulation dissociates fronto-visual theta lateralization during visual selective attention.

KEY POINTS: Visual attention involves discrete multispectral oscillatory responses in visual and 'higher-order' prefrontal cortices. Prefrontal cortex laterality effects during visual selective attention are poorly characterized. High-definition transcranial direct current stimulation dynamically modulated right-lateralized fronto-visual theta oscillations compared to those observed in left fronto-visual pathways. Increased connectivity in right fronto-visual networks after stimulation of the left dorsolateral prefrontal cortex resulted in faster task performance in the context of distractors. Our findings show clear laterality effects in theta oscillatory activity along prefrontal-visual cortical pathways during visual selective attention. ABSTRACT: Studies of visual attention have implicated oscillatory activity in the recognition, protection and temporal organization of attended representations in visual cortices. These studies have also shown that higher-order regions such as the prefrontal cortex are critical to attentional processing, but far less is understood regarding prefrontal laterality differences in attention processing. To examine this, we selectively applied high-definition transcranial direct current stimulation (HD-tDCS) to the left or right dorsolateral prefrontal cortex (DLPFC). We predicted that HD-tDCS of the left versus right prefrontal cortex would differentially modulate performance on a visual selective attention task, and alter the underlying oscillatory network dynamics. Our randomized crossover design included 27 healthy adults that underwent three separate sessions of HD-tDCS (sham, left DLPFC and right DLPFC) for 20 min. Following stimulation, participants completed an attention protocol during magnetoencephalography. The resulting oscillatory dynamics were imaged using beamforming, and peak task-related neural activity was subjected to dynamic functional connectivity analyses to evaluate the impact of stimulation site (i.e. left and right DLPFC) on neural interactions. Our results indicated that HD-tDCS over the left DLPFC differentially modulated right fronto-visual functional connectivity within the theta band compared to HD-tDCS of the right DLPFC and further, specifically modulated the oscillatory response for detecting targets among an array of distractors. Importantly, these findings provide network-specific insight into the complex oscillatory mechanisms serving visual selective attention.

Altered neural dynamics in occipital cortices serving visual-spatial processing in heavy alcohol users.

BACKGROUND: Visual-spatial processing deficits have been previously linked to heavy alcohol use, but the underlying neurological mechanisms are poorly understood. Neuroimaging studies have shown alcohol-related aberrations in occipital cortices that appear to be associated with these neuropsychological deficits in visual-spatial processing, however the neural dynamics underlying this altered processing remains unknown. METHODS: Twenty-three adults with high scores on the Alcohol Use Disorders Identification Test - Consumption (male: ⩾5, female: ⩾4) were compared to 30 demographically-matched controls with low Alcohol Use Disorders Identification Test - Consumption scores (⩽2). All participants completed a visual-spatial processing task while undergoing high-density magnetoencephalography. Time-frequency windows of interest were determined using a data-driven method, and spectrally-specific neural activity was imaged using a beamforming approach. Permutation testing of peak voxel time series was then used to statistically compare across groups. RESULTS: Participants with heavy alcohol use responded slower on the task and their performance was more variable. The magnetoencephalography data indicated strong theta (4-8 Hz), alpha (10-16 Hz), and gamma (62-72 Hz) responses in posterior brain regions across both groups. Following voxel time-series extraction, significant group differences were found in the left and right visual association cortices from about 375-550 ms post-stimulus, such that adults with heavy alcohol use had blunted alpha responses compared to controls. CONCLUSION: Individuals with heavy alcohol use exhibited aberrant occipital alpha activity during visual-spatial processing. These data are the first to show spectrally-specific differences during visual-spatial processing related to heavy alcohol use, and highlight alcohol's effect on systems-level neural activity.

Interactive effects of HIV and ageing on neural oscillations: independence from neuropsychological performance.

HIV infection is associated with increased age-related co-morbidities including cognitive deficits, leading to hypotheses of HIV-related premature or accelerated ageing. Impairments in selective attention and the underlying neural dynamics have been linked to HIV-associated neurocognitive disorder; however, the effect of ageing in this context is not yet understood. Thus, the current study aimed to identify the interactive effects of ageing and HIV on selective attention processing. A total of 165 participants (92 controls, 73 participants with HIV) performed a visual selective attention task while undergoing magnetoencephalography and were compared cross-sectionally. Spectrally specific oscillatory neural responses during task performance were imaged and linked with selective attention function. Reaction time on the task and regional neural activity were analysed with analysis of covariance (ANCOVA) models aimed at examining the age-by-HIV interaction term. Finally, these metrics were evaluated with respect to clinical measures such as global neuropsychological performance, duration of HIV infection and medication regimen. Reaction time analyses showed a significant HIV-by-age interaction, such that in controls older age was associated with greater susceptibility to attentional interference, while in participants with HIV, such susceptibility was uniformly high regardless of age. In regard to neural activity, theta-specific age-by-HIV interaction effects were found in the prefrontal and posterior parietal cortices. In participants with HIV, neuropsychological performance was associated with susceptibility to attentional interference, while time since HIV diagnosis was associated with parietal activity above and beyond global neuropsychological performance. Finally, current efavirenz therapy was also related to increased parietal interference activity. In conclusion, susceptibility to attentional interference in younger participants with HIV approximated that of older controls, suggesting evidence of HIV-related premature ageing. Neural activity serving attention processing indicated compensatory recruitment of posterior parietal cortex as participants with HIV infection age, which was related to the duration of HIV infection and was independent of neuropsychological performance, suggesting an altered trajectory of neural function.

Association of Epigenetic Metrics of Biological Age With Cortical Thickness.

Importance: Magnetic resonance imaging (MRI) studies of aging adults have shown substantial intersubject variability across various brain metrics, and some of this variability is likely attributable to chronological age being an imprecise measure of age-related change. Accurately quantifying one's biological age could allow better quantification of healthy and pathological changes in the aging brain. Objective: To investigate the association of DNA methylation (DNAm)-based biological age with cortical thickness and to assess whether biological age acceleration compared with chronological age captures unique variance in cortical thinning. Design, Setting, and Participants: This cross-sectional study used high-resolution structural brain MRI data collected from a sample of healthy aging adults who were participating in a larger ongoing neuroimaging study that began in May 2014. This population-based study accrued participants from the greater Omaha, Nebraska, metropolitan area. One hundred sixty healthy adults were contacted for the MRI component, 82 of whom participated in both DNAm and MRI study components. Data analysis was performed from March to June 2019. Main Outcomes and Measures: Vertexwise cortical thickness, DNAm-based biological age, and biological age acceleration compared with chronological age were measured. A pair of multivariable regression models were computed in which cortical thickness was regressed on DNAm-based biological age, controlling for sex in the first model and also controlling for chronological age in the second model. Results: Seventy-nine adult participants (38 women; mean [SD] age, 43.82 [14.50] years; age range, 22-72 years) were included in all final analyses. Advancing biological age was correlated with cortical thinning across frontal, superior temporal, inferior parietal, and medial occipital regions. In addition, biological age acceleration relative to chronological age was associated with cortical thinning in orbitofrontal, superior and inferior temporal, somatosensory, parahippocampal, and fusiform regions. Specifically, for every 1 year of biological age acceleration, cortical thickness would be expected to decrease by 0.024 mm (95% CI, -0.04 to -0.01 mm) in the left orbitofrontal cortex (partial r, -0.34; P = .002), 0.014 mm (95% CI, -0.02 to -0.01 mm) in the left superior temporal gyrus (partial r, -0.36; P = .001), 0.015 mm (95% CI, -0.02 to -0.01 mm) in the left fusiform gyrus (partial r, -0.38; P = .001), 0.015 mm (95% CI, -0.02 to -0.01 mm) in the right fusiform gyrus (partial r, -0.43; P < .001), 0.019 mm (95% CI, -0.03 to -0.01 mm) in the right inferior temporal sulcus (partial r, -0.34; P = .002), and 0.011 mm (95% CI, -0.02 to -0.01 mm) in the right primary somatosensory cortex (partial r, -0.37; P = .001). Conclusions and Relevance: To our knowledge, this is the first study to investigate vertexwise cortical thickness in relation to DNAm-based biological age, and the findings suggest that this metric of biological age may yield additional insight on healthy and pathological cortical aging compared with standard measures of chronological age alone.

Age-related visual dynamics in HIV-infected adults with cognitive impairment.

OBJECTIVE: To investigate whether aging differentially affects neural activity serving visuospatial processing in a large functional neuroimaging study of HIV-infected participants and to determine whether such aging effects are attributable to differences in the duration of HIV infection. METHODS: A total of 170 participants, including 93 uninfected controls and 77 HIV-infected participants, underwent neuropsychological assessment followed by neuroimaging with magnetoencephalography (MEG). Time-frequency analysis of the MEG data followed by advanced image reconstruction of neural oscillatory activity and whole-brain statistical analyses were used to examine interactions between age, HIV infection, and cognitive status. Post hoc testing for a mediation effect of HIV infection duration on the relationship between age and neural activity was performed using a quasi-Bayesian approximation for significance testing. RESULTS: Cognitively impaired HIV-infected participants were distinguished from unimpaired HIV-infected and control participants by their unique association between age and gamma oscillations in the parieto-occipital cortex. This relationship between age and gamma was fully mediated by the duration of HIV infection in cognitively impaired participants. Impaired HIV-infected participants were also distinguished by their atypical relationship between alpha oscillations and age in the superior parietal cortex. CONCLUSIONS: Impaired HIV-infected participants exhibited markedly different relationships between age and neural responses in the parieto-occipital cortices relative to their peers. This suggests a differential effect of chronological aging on the neural bases of visuospatial processing in a cognitively impaired subset of HIV-infected adults. Some of these relationships were fully accounted for by differences in HIV infection duration, whereas others were more readily associated with aging.

Aberrant brain dynamics in neuroHIV: Evidence from magnetoencephalographic (MEG) imaging.

Magnetoencephalography (MEG) is a noninvasive, silent, and totally passive neurophysiological imaging method with excellent temporal resolution (~1ms) and good spatial precision (~3-5mm). While MEG studies of neuroHIV remain relatively rare, the number of studies per year has sharply increased recently and this trend will likely continue into the foreseeable future. The current in-depth review focuses on the studies that have been conducted to date, which include investigations of somatosensory and visual modalities, resting-state, as well as motor control and higher-level functions such as working memory and visual attention. The review begins with an introduction to the principles and methods of MEG, and then transitions to a review of each of the empirical studies that have been conducted to date, separated by sensory modality for the basic studies and cognitive domain for the higher-level investigations. As such, this review attempts to be exhaustive in its coverage of empirical MEG studies of neuroHIV. Across studies major themes emerge including aberrant neural oscillatory activity in HIV-infected adults, both in primary sensory regions of the brain and higher-order executive regions. Many studies have also connected the amplitude of neural oscillations to behavioral and/or neuropsychological function in the study population, making a vital connection to performance and improving the veracity of the findings. One conspicuous emerging area is the use of MEG to distinguish cognitively-impaired from unimpaired HIV-infected adults, with major success reported and future studies sure to come. The review concludes with a summary of findings and suggested focus areas for future studies.