Changes in Brain Activation Patterns During Working Memory Tasks in People With Post-COVID Condition and Persistent Neuropsychiatric Symptoms.

BACKGROUND AND OBJECTIVES: Post-COVID condition (PCC) is common and often involves neuropsychiatric symptoms. This study aimed to use blood oxygenation level-dependent fMRI (BOLD-fMRI) to assess whether participants with PCC had abnormal brain activation during working memory (WM) and whether the abnormal brain activation could predict cognitive performance, motor function, or psychiatric symptoms. METHODS: The participants with PCC had documented coronavirus disease 2019 (COVID-19) at least 6 weeks before enrollment. Healthy control participants had no prior history of COVID-19 and negative tests for severe acute respiratory syndrome coronavirus 2. Participants were assessed using 3 NIH Toolbox (NIHTB) batteries for Cognition (NIHTB-CB), Emotion (NIHTB-EB), and Motor function (NIHTB-MB) and selected tests from the Patient-Reported Outcomes Measurement Information System (PROMIS). Each had BOLD-fMRI at 3T, during WM (N-back) tasks with increasing attentional/WM load. RESULTS: One hundred sixty-nine participants were screened; 50 fulfilled the study criteria and had complete and usable data sets for this cross-sectional cohort study. Twenty-nine participants with PCC were diagnosed with COVID-19 242 ± 156 days earlier; they had similar ages (42 ± 12 vs 41 ± 12 years), gender proportion (65% vs 57%), racial/ethnic distribution, handedness, education, and socioeconomic status, as the 21 uninfected healthy controls. Despite the high prevalence of memory (79%) and concentration (93%) complaints, the PCC group had similar performance on the NIHTB-CB as the controls. However, participants with PCC had greater brain activation than the controls across the network (false discovery rate-corrected p = 0.003, Tmax = 4.17), with greater activation in the right superior frontal gyrus (p = 0.009, Cohen d = 0.81, 95% CI 0.15-1.46) but lesser deactivation in the default mode regions (p = 0.001, d = 1.03, 95% CI 0.61-1.99). Compared with controls, participants with PCC also had poorer dexterity and endurance on the NIHTB-MB, higher T scores for negative affect and perceived stress, but lower T scores for psychological well-being on the NIHTB-EB, as well as more pain symptoms and poorer mental and physical health on measures from the PROMIS. Greater brain activation predicted poorer scores on measures that were abnormal on the NIHTB-EB. DISCUSSION: Participants with PCC and neuropsychiatric symptoms demonstrated compensatory neural processes with greater usage of alternate brain regions, and reorganized networks, to maintain normal performance during WM tasks. BOLD-fMRI was sensitive for detecting brain abnormalities that correlated with various quantitative neuropsychiatric symptoms.

Impact of active and latent concerns about COVID-19 on attention.

The interactions between emotion and attention are complex due to the multifaceted nature of attention. Adding to this complexity, the COVID-19 pandemic has altered the emotional landscape, broadly heightening health and financial concerns. Can the heightened concerns about COVID-19 impair one or more of the components of attention? To explore the connection between heightened concerns about COVID-19 and attention, in a preregistered study, we collected survey responses from 234 participants assessing levels of concerns surrounding COVID-19, followed by four psychophysics tasks hypothesized to tap into different aspects of attention: visual search, working memory, sustained attention, and cognitive control. We also measured task-unrelated thoughts. Results showed that task-unrelated thoughts, but not survey reports of concern levels, negatively correlated with sustained attention and cognitive control, while visual search and working memory remained robust to task-unrelated thoughts and survey-indicated concern levels. As a whole, these findings suggest that being concerned about COVID-19 does not interfere with cognitive function unless the concerns are active in the form of task-unrelated thoughts.

Intermittent theta burst stimulation over the parietal cortex has a significant neural effect on working memory.

The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta-burst stimulation (iTBS) can improve WM. In this within-subject randomized controlled study, under the guidance of fMRI-identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K-score were then calculated to reflect neural and behavioral WM improvement. Repeated-measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere-by-iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps <.05). In terms of the behavioral results, significant K score changes after real iTBS were observed for two conditions, but a repeated-measures ANOVA showed a nonsignificant main effect of iTBS (p = .826). These results indicate that the current iTBS protocol is a promising way to improve WM capability based on the neural indicator (CDA) but further optimization is needed to produce a behavioral effect.

Computer-assisted instruction versus inquiry-based learning: The importance of working memory capacity.

The Covid-19 pandemic has led millions of students worldwide to intensify their use of digital education. This massive change is not reflected by the scant scientific research on the effectiveness of methods relying on digital learning compared to other innovative and more popular methods involving face-to-face interactions. Here, we tested the effectiveness of computer-assisted instruction (CAI) in Science and Technology compared to inquiry-based learning (IBL), another modern method which, however, requires students to interact with each other in the classroom. Our research also considered socio-cognitive factors-working memory (WM), socioeconomic status (SES), and academic self-concept (ASC)-known to predict academic performance but usually ignored in research on IBL and CAI. Five hundred and nine middle-school students, a fairly high sample size compared with relevant studies, received either IBL or CAI for a period varying from four to ten weeks prior to the Covid-19 events. After controlling for students' prior knowledge and socio-cognitive factors, multilevel modelling showed that CAI was more effective than IBL. Although CAI-related benefits were stable across students' SES and ASC, they were particularly pronounced for those with higher WM capacity. While indicating the need to adapt CAI for students with poorer WM, these findings further justify the use of CAI both in normal times (without excluding other methods) and during pandemic episodes.

Causal role of frontal-midline theta in cognitive effort: a pilot study.

Frontal-midline theta (FMT) oscillations are increased in amplitude during cognitive control tasks. Since these tasks often conflate cognitive control and cognitive effort, it remains unknown if FMT amplitude maps onto cognitive control or effort. To address this gap, we utilized the glucose facilitation effect to manipulate cognitive effort without changing cognitive control demands. We performed a single-blind, crossover human study in which we provided participants with a glucose drink (control session: volume-matched water) to reduce cognitive effort and improve performance on a visuospatial working memory task. Following glucose consumption, participants performed the working memory task at multiple time points of a 3-h window to sample across the rise and fall of blood glucose. Using high-density electroencephalography (EEG), we calculated FMT amplitude during the delay period of the working memory task. Source localization analysis revealed that FMT oscillations originated from bilateral prefrontal cortex. We found that glucose increased working memory accuracy during the high working memory load condition but decreased FMT amplitude. The decrease in FMT amplitude coincided with both peak blood glucose elevation and peak performance enhancement for glucose relative to water. Therefore, the positive association between glucose consumption and task performance provided causal evidence that the amplitude of FMT oscillations may correspond to cognitive effort, rather than cognitive control. Due to the COVID-19 pandemic, data collection was terminated prematurely; the preliminary nature of these findings due to small sample size should be contextualized by rigorous experimental design and use of a novel causal perturbation to dissociate cognitive effort and cognitive control.NEW & NOTEWORTHY We investigated whether frontal-midline theta (FMT) oscillations tracked with cognitive control or cognitive effort by simultaneous manipulation of cognitive control demands in a working memory task and causal perturbation of cognitive effort using glucose consumption. Facilitation of performance from glucose consumption corresponded with decreased FMT amplitude, which provided preliminary causal evidence for a relationship between FMT amplitude with cognitive effort.

Persistent COVID-19-associated neurocognitive symptoms in non-hospitalized patients.

As cases of coronavirus disease 2019 (COVID-19) mount worldwide, attention is needed on potential long-term neurologic impacts for the majority of patients who experience mild to moderate illness managed as outpatients. To date, there has not been discussion of persistent neurocognitive deficits in patients with milder COVID-19. We present two cases of non-hospitalized patients recovering from COVID-19 with persistent neurocognitive symptoms. Commonly used cognitive screens were normal, while more detailed testing revealed working memory and executive functioning deficits. An observational cohort study of individuals recovering from COVID-19 (14 or more days following symptom onset) identified that among the first 100 individuals enrolled, 14 were non-hospitalized patients reporting persistent cognitive issues. These 14 participants had a median age of 39 years (interquartile range: 35-56), and cognitive symptoms were present for at least a median of 98 days (interquartile range: 71-120 following acute COVID-19 symptoms); no participants with follow-up evaluation reported symptom resolution. We discuss potential mechanisms to be explored in future studies, including direct viral effects, indirect consequences of immune activation, and immune dysregulation causing auto-antibody production.

Working memory capacity predicts individual differences in social-distancing compliance during the COVID-19 pandemic in the United States.

Noncompliance with social distancing during the early stage of the coronavirus disease 2019 (COVID-19) pandemic poses a great challenge to the public health system. These noncompliance behaviors partly reflect people's concerns for the inherent costs of social distancing while discounting its public health benefits. We propose that this oversight may be associated with the limitation in one's mental capacity to simultaneously retain multiple pieces of information in working memory (WM) for rational decision making that leads to social-distancing compliance. We tested this hypothesis in 850 United States residents during the first 2 wk following the presidential declaration of national emergency because of the COVID-19 pandemic. We found that participants' social-distancing compliance at this initial stage could be predicted by individual differences in WM capacity, partly due to increased awareness of benefits over costs of social distancing among higher WM capacity individuals. Critically, the unique contribution of WM capacity to the individual differences in social-distancing compliance could not be explained by other psychological and socioeconomic factors (e.g., moods, personality, education, and income levels). Furthermore, the critical role of WM capacity in social-distancing compliance can be generalized to the compliance with another set of rules for social interactions, namely the fairness norm, in Western cultures. Collectively, our data reveal contributions of a core cognitive process underlying social-distancing compliance during the early stage of the COVID-19 pandemic, highlighting a potential cognitive venue for developing strategies to mitigate a public health crisis.