Effects of Multisession Prefrontal Transcranial Direct Current Stimulation on Long-term Memory and Working Memory in Older Adults.

Transcranial direct current stimulation (tDCS) is a noninvasive form of electrical brain stimulation popularly used to augment the effects of working memory (WM) training. Although success has been mixed, some studies report enhancements in WM performance persisting days, weeks, or even months that are actually more reminiscent of consolidation effects typically observed in the long-term memory (LTM) domain, rather than WM improvements per se. Although tDCS has been often reported to enhance both WM and LTM, these effects have never been directly compared within the same study. However, given their considerable neural and behavioral overlap, this is a timely comparison to make. This study reports results from a multisession intervention in older adults comparing active and sham tDCS over the left dorsolateral pFC during training on both an n-back WM task and a word learning LTM task. We found strong and robust effects on LTM, but mixed effects on WM that only emerged for those with lower baseline ability. Importantly, mediation analyses showed an indirect effect of tDCS on WM that was mediated by improvements in consolidation. We conclude that tDCS over the left dorsolateral pFC can be used as an effective intervention to foster long-term learning and memory consolidation in aging, which can manifest in performance improvements across multiple memory domains.

How well do ordinary Americans forecast the growth of COVID-19?

Across three experiments (N = 1565), we investigated how forecasts about the spread of COVID 19 are impacted by data trends, and whether patterns of misestimation predict adherence to social-distancing guidelines. We also investigated how mode of data presentation influences forecasting of future cases by showing participants data on the number of COVID-19 cases from a 5-week period in either graphical, tabular, or text-only form. We consistently found that people shown tables produced more accurate forecasts compared to people shown line-graphs of the same data; yet people shown line-graphs were more confident in their estimates. These findings suggest that graphs engender false-confidence in the accuracy of forecasts, that people's forecasts of future cases have important implications for their attitudes concerning social distancing, and that tables may be better than graphs for informing the public about the trajectory of COVID-19.

Age differences in functional network reconfiguration with working memory training.

Demanding cognitive functions like working memory (WM) depend on functional brain networks being able to communicate efficiently while also maintaining some degree of modularity. Evidence suggests that aging can disrupt this balance between integration and modularity. In this study, we examined how cognitive training affects the integration and modularity of functional networks in older and younger adults. Twenty three younger and 23 older adults participated in 10 days of verbal WM training, leading to performance gains in both age groups. Older adults exhibited lower modularity overall and a greater decrement when switching from rest to task, compared to younger adults. Interestingly, younger but not older adults showed increased task-related modularity with training. Furthermore, whereas training increased efficiency within, and decreased participation of, the default-mode network for younger adults, it enhanced efficiency within a task-specific salience/sensorimotor network for older adults. Finally, training increased segregation of the default-mode from frontoparietal/salience and visual networks in younger adults, while it diffusely increased between-network connectivity in older adults. Thus, while younger adults increase network segregation with training, suggesting more automated processing, older adults persist in, and potentially amplify, a more integrated and costly global workspace, suggesting different age-related trajectories in functional network reorganization with WM training.

Post-training stimulation of the right dorsolateral prefrontal cortex impairs working memory training performance.

Research investigating transcranial direct current stimulation (tDCS) to enhance cognitive training augments both our understanding of its long-term effects on cognitive plasticity as well as potential applications to strengthen cognitive interventions. Previous work has demonstrated enhancement of working memory training while applying concurrent tDCS to the dorsolateral prefrontal cortex (DLPFC). However, the optimal stimulation parameters are still unknown. For example, the timing of tDCS delivery has been shown to be an influential variable that can interact with task learning. In the present study, we used tDCS to target the right DLPFC while participants trained on a visuospatial working memory task. We sought to compare the relative efficacy of online stimulation delivered during training to offline stimulation delivered either immediately before or afterwards. We were unable to replicate previously demonstrated benefits of online stimulation; however, we did find evidence that offline stimulation delivered after training can actually be detrimental to training performance relative to sham. We interpret our results in light of evidence suggesting a role of the right DLPFC in promoting memory interference, and conclude that while tDCS may be a promising tool to influence the results of cognitive training, more research and an abundance of caution are needed before fully endorsing its use for cognitive enhancement. This work suggests that effects can vary substantially in magnitude and direction between studies, and may be heavily dependent on a variety of intervention protocol parameters such as the timing and location of stimulation delivery, about which our understanding is still nascent.

Neural correlates of working memory training: Evidence for plasticity in older adults.

Brain activity typically increases with increasing working memory (WM) load, regardless of age, before reaching an apparent ceiling. However, older adults exhibit greater brain activity and reach ceiling at lower loads than younger adults, possibly reflecting compensation at lower loads and dysfunction at higher loads. We hypothesized that WM training would bolster neural efficiency, such that the activation peak would shift towards higher memory loads after training. Pre-training, older adults showed greater recruitment of the WM network than younger adults across all loads, with decline at the highest load. Ten days of adaptive training on a verbal WM task improved performance and led to greater brain responsiveness at higher loads for both groups. For older adults the activation peak shifted rightward towards higher loads. Finally, training increased task-related functional connectivity in older adults, both within the WM network and between this task-positive network and the task-negative/default-mode network. These results provide new evidence for functional plasticity with training in older adults and identify a potential signature of improvement at the neural level.

Neighborhood poverty predicts altered neural and behavioral response inhibition.

Socioeconomic disadvantage during childhood is associated with a myriad of negative adult outcomes. One mechanism through which disadvantage undermines positive outcomes may be by disrupting the development of self-control. The goal of the present study was to examine pathways from three key indicators of socioeconomic disadvantage - low family income, low maternal education, and neighborhood poverty - to neural and behavioral measures of response inhibition. We utilized data from a representative cohort of 215 twins (ages 7-18 years, 70% male) oversampled for exposure to disadvantage, who participated in the Michigan Twins Neurogenetics Study (MTwiNS), a study within the Michigan State University Twin Registry (MSUTR). Our child-friendly Go/No-Go task activated the bilateral inferior frontal gyrus (IFG), and activation during this task predicted behavioral inhibition performance, extending prior work on adults to youth. Critically, we also found that neighborhood poverty, assessed via geocoding, but not family income or maternal education, was associated with IFG activation, a finding that we replicated in an independent sample of disadvantaged youth. Further, we found that neighborhood poverty predicted response inhibition performance via its effect on IFG activation. These results provide the first mechanistic evidence that disadvantaged contexts may undermine self-control via their effect on the brain. The broader neighborhood, beyond familial contexts, may be critically important for this association, suggesting that contexts beyond the home have profound effects on the developing brain and behaviors critical for future health, wealth, and wellbeing.

Behavioral measures of attention and cognitive control during a new auditory working memory paradigm.

Proactive control is the ability to manipulate and maintain goal-relevant information within working memory (WM), allowing individuals to selectively attend to important information while inhibiting irrelevant distractions. Deficits in proactive control may cause multiple cognitive impairments seen in schizophrenia. However, studies of cognitive control have largely relied on visual tasks, even though the functional deficits in schizophrenia are more frequent and severe in the auditory domain (i.e., hallucinations). Hence, we developed an auditory analogue of a visual ignore/suppress paradigm. Healthy adults (N = 40) listened to a series of four letters (600-ms stimulus onset asynchrony) presented alternately to each ear, followed by a 3.2-s maintenance interval and a probe. Participants were directed either to selectively ignore (I) the to-be-presented letters at one ear, to suppress (S) letters already presented to one ear, or to remember (R) all presented letters. The critical cue was provided either before (I) or after (S) the encoding series, or simultaneously with the probe (R). The probes were encoding items presented to either the attended/not suppressed ear ("valid") or the ignored/suppressed ear ("lure"), or were not presented ("control"). Replicating prior findings during visual ignore/suppress tasks, response sensitivity and latency revealed poorer performance for lure than for control trials, particularly during the suppress condition. Shorter suppress than remember latencies suggested a behavioral advantage when discarding encoded items from WM. The paradigm-related internal consistencies and 1-week test-retest reliabilities (n = 38) were good to excellent. Our findings validate these auditory WM tasks as a reliable manipulation of proactive control and set the stage for studies with schizophrenia patients who experience auditory hallucinations.

Construct Validity of the Multi-Source Interference Task to Examine Attention in Heart Failure.

BACKGROUND: Patients with heart failure (HF) are at risk of cognitive dysfunction, including decreased directed attention. Directed attention is critical for performing daily activities including HF self-care by facilitating one to follow instructions or train-of-thought when there are interferences in which presented stimuli are in conflict with one another. The Multi-Source Interference Task (MSIT) is a computerized neuropsychological test that examines the function of the dorsal anterior cingulate cortex, the neurological substrate for directed attention. However, the MSIT has not been used in past HF studies. OBJECTIVE: The purpose of the study was to examine construct validity of the MSIT in HF. METHODS: Baseline data were obtained from a cognitive intervention study among patients with HF (n = 22) and age- and education-matched healthy adults (n = 20). Construct validity was evaluated using t tests to examine differences between patients with HF and healthy adults and congruent and incongruent MSIT trials. Pearson's correlations were computed to examine relationships between the MSIT and Trail-Making Test, Stroop Test, and Attentional Function Index. RESULTS: Compared with healthy adults, patients with HF demonstrated worse performance (i.e., slower response times and higher error rates) on MSIT. Patients with HF had worse performance on MSIT incongruent trials than congruent trials. Interference z scores of MSIT did not correlate with Trail-Making Tests A and B and Stroop Test interference z scores, but the MSIT interference z scores correlated with perceived attention function measured by Attentional Function Index. DISCUSSION: Construct validity of the MSIT was supported, in part, among patients with HF. The MSIT is a sensitive measure of detecting worse directed attention among patients with HF compared with healthy adults. The preliminary findings support the use of the MSIT as a measure of directed attention in HF. Confirmation is warranted for current findings in larger samples.

Stable long-range interhemispheric coordination is supported by direct anatomical projections.

The functional interaction between the brain's two hemispheres includes a unique set of connections between corresponding regions in opposite hemispheres (i.e., homotopic regions) that are consistently reported to be exceptionally strong compared with other interhemispheric (i.e., heterotopic) connections. The strength of homotopic functional connectivity (FC) is thought to be mediated by the regions' shared functional roles and their structural connectivity. Recently, homotopic FC was reported to be stable over time despite the presence of dynamic FC across both intrahemispheric and heterotopic connections. Here we build on this work by considering whether homotopic FC is also stable across conditions. We additionally test the hypothesis that strong and stable homotopic FC is supported by the underlying structural connectivity. Consistent with previous findings, interhemispheric FC between homotopic regions were significantly stronger in both humans and macaques. Across conditions, homotopic FC was most resistant to change and therefore was more stable than heterotopic or intrahemispheric connections. Across time, homotopic FC had significantly greater temporal stability than other types of connections. Temporal stability of homotopic FC was facilitated by direct anatomical projections. Importantly, temporal stability varied with the change in conductive properties of callosal axons along the anterior-posterior axis. Taken together, these findings suggest a notable role for the corpus callosum in maintaining stable functional communication between hemispheres.

Individual Differences and Long-term Consequences of tDCS-augmented Cognitive Training.

A great deal of interest surrounds the use of transcranial direct current stimulation (tDCS) to augment cognitive training. However, effects are inconsistent across studies, and meta-analytic evidence is mixed, especially for healthy, young adults. One major source of this inconsistency is individual differences among the participants, but these differences are rarely examined in the context of combined training/stimulation studies. In addition, it is unclear how long the effects of stimulation last, even in successful interventions. Some studies make use of follow-up assessments, but very few have measured performance more than a few months after an intervention. Here, we utilized data from a previous study of tDCS and cognitive training [Au, J., Katz, B., Buschkuehl, M., Bunarjo, K., Senger, T., Zabel, C., et al. Enhancing working memory training with transcranial direct current stimulation. Journal of Cognitive Neuroscience, 28, 1419-1432, 2016] in which participants trained on a working memory task over 7 days while receiving active or sham tDCS. A new, longer-term follow-up to assess later performance was conducted, and additional participants were added so that the sham condition was better powered. We assessed baseline cognitive ability, gender, training site, and motivation level and found significant interactions between both baseline ability and motivation with condition (active or sham) in models predicting training gain. In addition, the improvements in the active condition versus sham condition appear to be stable even as long as a year after the original intervention.

Randomized Crossover Study of the Natural Restorative Environment Intervention to Improve Attention and Mood in Heart Failure.

BACKGROUND: In heart failure (HF), attention may be decreased because of lowered cerebral blood flow and increased attentional demands needed for self-care. OBJECTIVE: Guided by the Attention Restoration Theory, the objective was to test the efficacy of the natural restorative environment (NRE) intervention on improving attention and mood among HF patients and healthy adults. METHODS: A randomized crossover pilot study was conducted among 20 HF patients and an age- and education-matched comparison group of 20 healthy adults to test the efficacy of the NRE intervention compared with an active control intervention. Neuropsychological tests were administered to examine attention, particularly attention span, sustained attention, directed attention, and attention switching, at before and after the intervention. Mood was measured with the Positive and Negative Affect Schedule. RESULTS: No significant differences were found in attention and mood after the NRE intervention compared with the control intervention among the HF patients and the healthy adults. In analyses with HF patients and healthy adults combined (n = 40), significant differences were found. Compared with the control intervention, sustained attention improved after the NRE intervention (P = .001) regardless of the presence of HF. Compared with the healthy adults, HF patients performed significantly worse on attention switching after the control intervention (P = .045). CONCLUSIONS: The NRE intervention may be efficacious in improving sustained attention in HF patients. Future studies are needed to enhance the NRE intervention to be more efficacious and tailored for HF patients and test the efficacy in a larger sample of HF patients.

Effects of proactive interference on non-verbal working memory.

Working memory (WM) is a cognitive system responsible for actively maintaining and processing relevant information and is central to successful cognition. A process critical to WM is the resolution of proactive interference (PI), which involves suppressing memory intrusions from prior memories that are no longer relevant. Most studies that have examined resistance to PI in a process-pure fashion used verbal material. By contrast, studies using non-verbal material are scarce, and it remains unclear whether the effect of PI is domain-general or whether it applies solely to the verbal domain. The aim of the present study was to examine the effect of PI in visual WM using both objects with high and low nameability. Using a Directed-Forgetting paradigm, we varied discriminability between WM items on two dimensions, one verbal (high-nameability vs. low-nameability objects) and one perceptual (colored vs. gray objects). As in previous studies using verbal material, effects of PI were found with object stimuli, even after controlling for verbal labels being used (i.e., low-nameability condition). We also found that the addition of distinctive features (color, verbal label) increased performance in rejecting intrusion probes, most likely through an increase in discriminability between content-context bindings in WM.

Enhancing Working Memory Training with Transcranial Direct Current Stimulation.

Working memory (WM) is a fundamental cognitive ability that supports complex thought but is limited in capacity. Thus, WM training interventions have become very popular as a means of potentially improving WM-related skills. Another promising intervention that has gained increasing traction in recent years is transcranial direct current stimulation (tDCS), a noninvasive form of brain stimulation that can modulate cortical excitability and temporarily increase brain plasticity. As such, it has the potential to boost learning and enhance performance on cognitive tasks. This study assessed the efficacy of tDCS to supplement WM training. Sixty-two participants were randomized to receive either right prefrontal, left prefrontal, or sham stimulation with concurrent visuospatial WM training over the course of seven training sessions. Results showed that tDCS enhanced training performance, which was strikingly preserved several months after training completion. Furthermore, we observed stronger effects when tDCS was spaced over a weekend break relative to consecutive daily training, and we also demonstrated selective transfer in the right prefrontal group to nontrained tasks of visual and spatial WM. These findings shed light on how tDCS may be leveraged as a tool to enhance performance on WM-intensive learning tasks.

Frontal-medial temporal interactions mediate transitions among representational states in short-term memory.

Short-term memory (STM), the brief maintenance of information in the absence of external stimulation, is central to higher-level cognition. Behavioral and neural data indicate that information maintained in STM can be represented in qualitatively distinct states. These states include a single chunk held in the focus of attention available for immediate processing (the "focus"), a capacity-limited set of additional actively maintained items that the focus can access (the "active state"), and passively maintained items (the "passive state"). Little is known about how information is shifted among these states. Here, we used fMRI in humans to examine the neural correlates of shifting information among representational states of STM. We used a paradigm that has demonstrated dissociable performance costs associated with shifting the focus among active items and switching sets of items between active and passive states. Behavioral results confirmed distinct behavioral costs associated with different representational states. Neural results indicated that the caudal superior frontal sulcus (cSFS), in the vicinity of the frontal eye fields, was associated with shifting the focus, consistent with the role of this region in internal and external attention. By contrast, the ventral premotor cortex (PMv) was associated with shifting between active and passive states. Increased cSFS-medial temporal lobe (MTL) connectivity was associated with shifting the focus, while cSFS-MTL connectivity was disrupted when the active state was changed. By contrast, PMv-MTL connectivity increased when the active state was switched. These data indicate that dissociable frontal-MTL interactions mediate shifts of information among different representational states in STM.

Dissociable functional networks of the human dentate nucleus.

The cerebellar dentate nucleus has been reported to project to motor and prefrontal cortical regions in nonhuman primates from 2 anatomically distinct areas. However, despite a wealth of human neuroimaging data implicating the cerebellum in motor and cognitive behaviors, evidence of dissociable motor and cognitive networks comprising the human dentate is lacking. To investigate the existence of these 2 networks in the human brain, we used resting-state functional connectivity magnetic resonance imaging. The resting-state fMRI signal was extracted from regions of interest in the dorsal and ventral dentate nucleus. We report a "motor" network involving the dorsal dentate, anterior regions of the cerebellum, and the precentral gyrus, and a "cognitive" network involving the ventral dentate, Crus I, and prefrontal cortex. The existence of these 2 distinct networks supports the notion that cerebellar involvement in cognitive tasks is above and beyond that associated with motor response components.

Does resting-state connectivity reflect depressive rumination? A tale of two analyses.

Major Depressive Disorder (MDD) is characterized by rumination. Prior research suggests that resting-state brain activation reflects rumination when depressed individuals are not task engaged. However, no study has directly tested this. Here we investigated whether resting-state epochs differ from induced ruminative states for healthy and depressed individuals. Most previous research on resting-state networks comes from seed-based analyses with the posterior cingulate cortex (PCC). By contrast, we examined resting state connectivity by using the complete multivariate connectivity profile (i.e., connections across all brain nodes) and by comparing these results to seeded analyses. We find that unconstrained resting-state intervals differ from active rumination states in strength of connectivity and that overall connectivity was higher for healthy vs. depressed individuals. Relationships between connectivity and subjective mood (i.e., behavior) were strongly observed during induced rumination epochs. Furthermore, connectivity patterns that related to subjective mood were strikingly different for MDD and healthy control (HC) groups suggesting different mood regulation mechanisms.

Neural effects of short-term training on working memory.

Working memory training has been the focus of intense research interest. Despite accumulating behavioral work, knowledge about the neural mechanisms underlying training effects is scarce. Here, we show that 7 days of training on an n-back task led to substantial performance improvements in the trained task; furthermore, the experimental group showed cross-modal transfer, as compared with an active control group. In addition, there were two neural effects that emerged as a function of training: first, increased perfusion during task performance in selected regions, reflecting a neural response to cope with high task demand; second, increased blood flow at rest in regions where training effects were apparent. We also found that perfusion at rest was correlated with task proficiency, probably reflecting an improved neural readiness to perform. Our findings are discussed within the context of the available neuroimaging literature on n-back training.

Methylphenidate blocks effort-induced depletion of regulatory control in healthy volunteers.

A recent wave of studies--more than 100 conducted over the last decade--has shown that exerting effort at controlling impulses or behavioral tendencies leaves a person depleted and less able to engage in subsequent rounds of regulation. Regulatory depletion is thought to play an important role in everyday problems (e.g., excessive spending, overeating) as well as psychiatric conditions, but its neurophysiological basis is poorly understood. Using a placebo-controlled, double-blind design, we demonstrated that the psychostimulant methylphenidate (commonly known as Ritalin), a catecholamine reuptake blocker that increases dopamine and norepinephrine at the synaptic cleft, fully blocks effort-induced depletion of regulatory control. Spectral analysis of trial-by-trial reaction times revealed specificity of methylphenidate effects on regulatory depletion in the slow-4 frequency band. This band is associated with the operation of resting-state brain networks that produce mind wandering, which raises potential connections between our results and recent brain-network-based models of control over attention.

A meta-analysis of executive components of working memory.

Working memory (WM) enables the online maintenance and manipulation of information and is central to intelligent cognitive functioning. Much research has investigated executive processes of WM in order to understand the operations that make WM "work." However, there is yet little consensus regarding how executive processes of WM are organized. Here, we used quantitative meta-analysis to summarize data from 36 experiments that examined executive processes of WM. Experiments were categorized into 4 component functions central to WM: protecting WM from external distraction (distractor resistance), preventing irrelevant memories from intruding into WM (intrusion resistance), shifting attention within WM (shifting), and updating the contents of WM (updating). Data were also sorted by content (verbal, spatial, object). Meta-analytic results suggested that rather than dissociating into distinct functions, 2 separate frontal regions were recruited across diverse executive demands. One region was located dorsally in the caudal superior frontal sulcus and was especially sensitive to spatial content. The other was located laterally in the midlateral prefrontal cortex and showed sensitivity to nonspatial content. We propose that dorsal-"where"/ventral-"what" frameworks that have been applied to WM maintenance also apply to executive processes of WM. Hence, WM can largely be simplified to a dual selection model.

The role of individual differences in cognitive training and transfer.

Working memory (WM) training has recently become a topic of intense interest and controversy. Although several recent studies have reported near- and far-transfer effects as a result of training WM-related skills, others have failed to show far transfer, suggesting that generalization effects are elusive. Also, many of the earlier intervention attempts have been criticized on methodological grounds. The present study resolves some of the methodological limitations of previous studies and also considers individual differences as potential explanations for the differing transfer effects across studies. We recruited intrinsically motivated participants and assessed their need for cognition (NFC; Cacioppo & Petty Journal of Personality and Social Psychology 42:116-131, 1982) and their implicit theories of intelligence (Dweck, 1999) prior to training. We assessed the efficacy of two WM interventions by comparing participants' improvements on a battery of fluid intelligence tests against those of an active control group. We observed that transfer to a composite measure of fluid reasoning resulted from both WM interventions. In addition, we uncovered factors that contributed to training success, including motivation, need for cognition, preexisting ability, and implicit theories about intelligence.