GABAergic inhibition shapes behavior and neural dynamics in human visual working memory.

Neuronal inhibition, primarily mediated by GABAergic neurotransmission, is crucial for brain development and healthy cognition. Gamma-aminobutyric acid concentration levels in sensory areas have been shown to correlate with hemodynamic and oscillatory neuronal responses. How these measures relate to one another during working memory, a higher-order cognitive process, is still poorly understood. We address this gap by collecting magnetoencephalography, functional magnetic resonance imaging, and Flumazenil positron emission tomography data within the same subject cohort using an n-back working-memory paradigm. By probing the relationship between GABAA receptor distribution, neural oscillations, and Blood Oxygen Level Dependent (BOLD) modulations, we found that GABAA receptor density in higher-order cortical areas predicted the reaction times on the working-memory task and correlated positively with the peak frequency of gamma power modulations and negatively with BOLD amplitude. These findings support and extend theories linking gamma oscillations and hemodynamic responses to gamma-aminobutyric acid neurotransmission and to the excitation-inhibition balance and cognitive performance in humans. Considering the small sample size of the study, future studies should test whether these findings also hold for other, larger cohorts as well as to examine in detail how the GABAergic system and neural fluctuations jointly support working-memory task performance.

Brain correlates of attentional load processing reflect degree of bilingual engagement: Evidence from EEG.

The present study uses electroencephalography (EEG) with an N-back task (0-, 1-, and 2-back) to investigate if and how individual bilingual experiences modulate brain activity and cognitive processes. The N-back is an especially appropriate task given recent proposals situating bilingual effects on neurocognition within the broader attentional control system (Bialystok and Craik, 2022). Beyond its working memory component, the N-Back task builds in complexity incrementally, progressively taxing the attentional system. EEG, behavioral and language/social background data were collected from 60 bilinguals. Two cognitive loads were calculated: low (1-back minus 0-back) and high (2-back minus 0-back). Behavioral performance and brain recruitment were modeled as a function of individual differences in bilingual engagement. We predicted task performance as modulated by bilingual engagement would reflect cognitive demands of increased complexity: slower reaction times and lower accuracy, and increase in theta, decrease in alpha and modulated N2/P3 amplitudes. The data show no modulation of the expected behavioral effects by degree of bilingual engagement. However, individual differences analyses reveal significant correlations between non-societal language use in Social contexts and alpha in the low cognitive load condition and age of acquisition of the L2/2L1 with theta in the high cognitive load. These findings lend some initial support to Bialystok and Craik (2022), showing how certain adaptations at the brain level take place in order to deal with the cognitive demands associated with variations in bilingual language experience and increases in attentional load. Furthermore, the present data highlight how these effects can play out differentially depending on cognitive testing/modalities - that is, effects were found at the TFR level but not behaviorally or in the ERPs, showing how the choice of analysis can be deterministic when investigating bilingual effects.

Functional near-infrared spectroscopy evidence of cognitive-motor interference in different dual tasks.

Dual tasks (DTs) combining walking with a cognitive task can cause various levels of cognitive-motor interference, depending on which brain resources are recruited in each case. However, the brain activation and functional connectivity underlying cognitive-motor interferences remain to be elucidated. Therefore, this study investigated the neural correlation during different DT conditions in 40 healthy young adults (mean age: 27.53 years, 28 women). The DTs included walking during subtraction or N-Back tasks. Cognitive-motor interference was calculated, and brain activation and functional connectivity were analysed. Portable functional near-infrared spectroscopy was utilized to monitor haemodynamics in the prefrontal cortex (PFC), motor cortex and parietal cortex during each task. Walking interference (decrease in walking speed during DT) was greater than cognitive interference (decrease in cognitive performance during DT), regardless of the type of task. Brain activation in the bilateral PFC and parietal cortex was greater for walking during subtraction than for standing subtraction. Furthermore, brain activation was higher in the bilateral motor and parietal and PFCs for walking during subtraction than for walking alone, but only increased in the PFC for walking during N-Back. Coherence between the bilateral lateral PFC and between the left lateral PFC and left motor cortex was significantly greater for walking during 2-Back than for walking. The PFC, a critical brain region for organizing cognitive and motor functions, played a crucial role in integrating information coming from multiple brain networks required for completing DTs. Therefore, the PFC could be a potential target for the modulation and improvement of cognitive-motor functions during neurorehabilitation.

Phenylephrine alters phase synchronization between cerebral blood velocity and blood pressure in ME/CFS with orthostatic intolerance.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with orthostatic intolerance (OI) is characterized by neurocognitive deficits perhaps related to upright hypocapnia and loss of cerebral autoregulation (CA). We performed N-back neurocognition testing and calculated the phase synchronization index (PhSI) between arterial pressure (AP) and cerebral blood velocity (CBV) as a time-dependent measurement of cerebral autoregulation in 11 control (mean age = 24.1 yr) and 15 patients with ME/CFS (mean age = 21.8 yr). All patients with ME/CFS had postural tachycardia syndrome (POTS). A 10-min 60° head-up tilt (HUT) significantly increased heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decreased end-tidal CO2 (ETCO2; 33.9 ± 1.1 vs. 42.8 ± 1.2 Torr, P < 0.05) in ME/CFS versus control. In ME/CFS, HUT significantly decreased CBV compared with control (-22.5% vs. -8.7%, P < 0.005). To mitigate the orthostatic CBV reduction, we administered supplemental CO2, phenylephrine, and acetazolamide and performed N-back testing supine and during HUT. Only phenylephrine corrected the orthostatic decrease in neurocognition by reverting % correct n = 4 N-back during HUT in ME/CFS similar to control (ME/CFS = 38.5 ± 5.5 vs. ME/CFS + PE= 65.6 ± 5.7 vs. Control 56.9 ± 7.5). HUT in ME/CFS resulted in increased PhSI values indicating decreased CA. Although CO2 and acetazolamide had no effect on PhSI in ME/CFS, phenylephrine caused a significant reduction in PhSI (ME/CFS = 0.80 ± 0.03 vs. ME/CFS + PE= 0.69 ± 0.04, P < 0.05) and improved cerebral autoregulation. Thus, PE improved neurocognitive function in patients with ME/CFS, perhaps related to improved neurovascular coupling, cerebral autoregulation, and maintenance of CBV.NEW & NOTEWORTHY We evaluated cognitive function before and after CO2, acetazolamide, and phenylephrine, which mitigate orthostatic reductions in cerebral blood velocity. Neither CO2 nor acetazolamide affected N-back testing (% correct answers) during an orthostatic challenge. Only phenylephrine improved upright N-back performance in ME/CFS, as it both blocked hyperventilation and increased CO2 significantly compared with those untreated. And only phenylephrine resulted in improved PSI values in both ME/CFS and control while upright, suggesting improved cerebral autoregulation.

Stimulus-related modulation in the 1/f spectral slope suggests an impaired inhibition during a working memory task in people with multiple sclerosis.

BACKGROUND: An imbalance of excitatory and inhibitory synaptic transmission in multiple sclerosis (MS) may lead to cognitive impairment, such as impaired working memory. The 1/f slope of electroencephalography/magnetoencephalography (EEG/MEG) power spectra is shown to be a non-invasive proxy of excitation/inhibition balance. A flatter slope is associated with higher excitation/lower inhibition. OBJECTIVES: To assess the 1/f slope modulation induced by stimulus and its association with behavioral and cognitive measures. METHODS: We analyzed MEG recordings of 38 healthy controls (HCs) and 79 people with multiple sclerosis (pwMS) while performing an n-back task including target and distractor stimuli. Target trials require an answer, while distractor trials do not. We computed the 1/f spectral slope through the fitting oscillations and one over f (FOOOF) algorithm within the time windows 1 second before and after each stimulus presentation. RESULTS: We observed a flatter 1/f slope after distractor stimuli in pwMS compared to HCs. The 1/f slope was significantly steeper after stimulus for both HCs and pwMS and was significantly correlated with reaction times. This modulation in 1/f slope was significantly correlated with visuospatial memory assessed by the BVMT-R test. CONCLUSION: Our results suggest possible inhibitory mechanism deficits in pwMS during a working memory task.

Joint contributions from brain activity and activity-independent functional connectivity to working memory aging.

Working memory (WM) impairment has been well characterized in normal aging. Various studies have explored changes in either the regional activity or the interregional connectivity underlying the aging process of WM. We proposed that brain activity and connectivity would independently alter with aging and affect WM performance. WM was assessed with a classical N-back task during functional magnetic resonance imaging in a community-based sample comprising 168 elderly subjects (aged 55-86 years old). Following the rationale of background functional connectivity, we assessed age-related alterations in brain activity and seed-based interregional connectivity independently. Analyses revealed age-related decrease in positive activity of the inferior parietal lobule (IPL) and an increase in the negative activity of the ventral anterior cingulate cortex (ACC), and the local functional dysfunctions were accompanied by alterations in their connectivity to other cortical regions. Importantly, regional activity impairments in the IPL and ACC could mediate age-related effects on accuracy rate and reaction time, respectively, and those effects were further counterbalanced by enhancement of their background functional connectivity. We thus claimed that age-induced alterations in regional activity and interregional connectivity occurred independently and contributed to WM changes in aging. Our findings presented the way brain activity and functional connectivity interact in the late adulthood, thus providing a new perspective for understanding WM and cognitive aging.

The effect of reward expectation on working memory of emotional faces under different levels of cognitive load: an ERP study.

Using event-related potentials (ERPs), this study examined the impact of reward expectations on working memory of emotional faces under different levels of cognitive load in a task combining the N-back paradigm and the reward expectation paradigm. The experiment involved presenting high- or low-reward cues followed by an N-back task for emotional faces with different loads. The accuracy results showed that under a high task load, both reward and emotion effects were significantly observed. However, these effects disappeared under a low task load. Analysis of the ERP data revealed that the early P2 and VPP components exhibited greater responses to fearful faces than to neutral faces. In the later stages, the P3 and LPP components showed greater reactions to high rewards than to low rewards. Additionally, the P2 component was found to be modulated by task load in relation to rewards, the EPN component demonstrated task load modulation with respect to emotions, and the N170 component showed an interaction effect between rewards and emotions. These findings imply that load regulates the reward effect and the emotional superiority effect in the process of working memory for emotional faces. In the cognitive processing of working memory, motivation and emotion jointly influence processing. Emotional factors have a greater impact in the early stage of processing, while motivation factors have a greater impact in the late stage of processing.

The characteristics of WM in individuals with depressive tendencies: A functional near-infrared spectroscopy (fNIRS) study.

Individuals with depressive tendencies are considered to be at high risk for the onset of depressive disorders. Currently, most research focuses on the impairment of working memory in patients with depression, while there is less attention paid to the WM of individuals with depressive tendencies, and their neural mechanisms underlying it are poorly understood. Therefore, this study focuses on the characteristics and neural mechanisms of WM in individuals with depressive tendencies. This study uses functional near-infrared spectroscopy (fNIRS) to monitor the concentration of Oxy-Hb in the prefrontal cortex and employs the n-back paradigm, designing three levels of load: 0, 1, and 2, to examine the characteristics of WM and its neural mechanisms in individuals with depressive tendencies. Behavioral results show that the accuracy rates of individuals with depressive tendencies is significantly lower than that of healthy individuals, and under the 0-back condition, the reaction time of individuals with depressive tendencies is significantly higher than that of healthy control individuals. Near-infrared results indicate that the activation level in the frontal pole and the dorsal lateral prefrontal cortex of individuals with depressive tendencies is significantly lower than that of healthy control individuals. The ß values of channels 2, 7, and 9 are significantly negatively correlated with the Beck Depression Inventory scores of the participants. The results suggest that the reduced activation of the frontal pole and dorsal lateral prefrontal cortex in individuals with depressive tendencies leads to poorer WM performance compared to healthy control individuals. This is a rare brain evidence of the characteristics of WM in individuals with depressive tendencies, which can provide a deeper understanding of the WM characteristics of individuals with depressive tendencies.

Aberrant brain dynamics in major depressive disorder during working memory task.

Working memory (WM) is a distributed and dynamic process, and WM deficits are recognized as one of the top-ranked endophenotype candidates for major depressive disorders (MDD). However, there is a lack of knowledge of brain temporal-spatial profile of WM deficits in MDD. We used the dynamical degree centrality (dDC) to investigate the whole-brain temporal-spatial profile in 40 MDD and 40 controls during an n-back task with 2 conditions (i.e., '0back' and '2back'). We explored the dDC temporal variability and clustered meta-stable states in 2 groups during different WM conditions. Pearson's correlation analysis was used to evaluate the relationship between the altered dynamics with clinical symptoms and WM performance. Compared with controls, under '2back vs. 0back' contrast, patients showed an elevated dDC variability in wide range of brain regions, including the middle frontal gyrus, orbital part of inferior frontal gyrus (IFGorb), hippocampus, and middle temporal gyrus. Furthermore, the increased dDC variability in the hippocampus and IFGorb correlated with worse WM performance. However, there were no significant group-related differences in the meta-stable states were observed. This study demonstrated the increased WM-related instability (i.e., the elevated dDC variability) was represented in MDD, and enhancing stability may help patients achieve better WM performance.

A domain-general frontoparietal network interacts with domain-preferential intermediate pathways to support working memory task.

Working memory (WM) is essential for cognition, but the underlying neural mechanisms remain elusive. From a hierarchical processing perspective, this paper proposed and tested a hypothesis that a domain-general network at the top of the WM hierarchy can interact with distinct domain-preferential intermediate circuits to support WM. Employing a novel N-back task, we first identified the posterior superior temporal gyrus (pSTG), middle temporal area (MT), and postcentral gyrus (PoCG) as intermediate regions for biological motion and shape motion processing, respectively. Using further psychophysiological interaction analyses, we delineated a frontal-parietal network (FPN) as the domain-general network. These results were further verified and extended by a delayed match to sample (DMS) task. Although the WM load-dependent and stimulus-free activations during the DMS delay phase confirm the role of FPN as a domain-general network to maintain information, the stimulus-dependent activations within this network during the DMS encoding phase suggest its involvement in the final stage of the hierarchical processing chains. In contrast, the load-dependent activations of intermediate regions in the N-back task highlight their further roles beyond perception in WM tasks. These results provide empirical evidence for a hierarchical processing model of WM and may have significant implications for WM training.