Working Memory Performance In Humans Research Articles

"Leader-Follower" Dynamic Perturbation Manipulates Multi-Item Working Memory in Humans.

Manipulating working memory (WM) is a central yet challenging notion. Previous studies suggest that WM items with varied memory strengths reactivate at different latencies, supporting a time-based mechanism. Motivated by this view, here we developed a purely bottom-up "Leader-Follower" behavioral approach to manipulate WM in humans. Specifically, task-irrelevant flickering color disks that are bound to each of the memorized items are presented during the delay period, and the ongoing luminance sequences of the color disks follow a Leader-Follower relationship, that is, a hundreds of milliseconds temporal lag. We show that this dynamic behavioral approach leads to better memory performance for the item associated with the temporally advanced luminance sequence (Leader) than the item with the temporally lagged luminance sequence (Follower), yet with limited effectiveness. Together, our findings constitute evidence for the essential role of temporal dynamics in WM operation and offer a promising, noninvasive WM manipulation approach.

Transcutaneous auricular vagus stimulation (taVNS) improves human working memory performance under sleep deprivation stress

Many human activities require high cognitive performance over long periods, while impairments induced by sleep deprivation influence various aspects of cognitive abilities, including working memory (WM), attention, and processing speed. Based on previous research, vagal nerve stimulation can modulate cognitive abilities, attention, and arousal. Two experiments were conducted to assess the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) to relieve the deleterious effects of sleep deprivation. In the first experiment, 35 participants completed N-back tasks at 8:00 a.m. for two consecutive days in a within-subject study. Then, the participants received either taVNS or earlobe stimulation (active control) intervention in two sessions at random orders after 24 h of sustained wakefulness. Then, they completed the N-back tasks again. In the second experiment, 30 participants completed the psychomotor vigilance task (PVT), and 32 completed the N-back tasks at 8:00 a.m. on the first and second days. Then, they received either taVNS or earlobe stimulation at random orders and finished the N-back and PVT tasks immediately after one hour. In Experiment 1, taVNS could significantly improve the accuracy rate of participants in spatial 3-back tasks compared to active control, which was consistent with experiment 2. However, taVNS did not specifically enhance PVT performance. Therefore, taVNS could be a powerful intervention for acute sleep deprivation as it can improve performance on high cognitive load tasks and is easy to administer.

(Lack of) Effects of noradrenergic stimulation on human working memory performance

RationaleWorking memory depends on prefrontal cortex functioning, which is particularly sensitive to levels of noradrenaline. Studies in non-human primates have shown that modest levels of noradrenaline improve working memory, and that higher levels of noradrenaline impair working memory performance. However, research in humans provided inconsistent findings concerning noradrenergic effects on working memory.ObjectiveThe present study aimed at assessing dose-dependent effects of yohimbine, an alpha-2 adrenoceptor antagonist, on working memory performance in healthy humans. We further aimed to explore a potential interactive effect between noradrenergic arousal and lack of control over aversive events on working memory performance.MethodsWe used a double-blind, fully crossed, placebo-controlled, between-subject design. Participants (N = 121) performed an adaptive n-back task before and after oral administration of either a placebo, 20 mg, or 40 mg yohimbine and a manipulation of controllability, during which participants could either learn to avoid electric shocks (controllability groups), had no instrumental control over shock administration (uncontrollability groups), or did not receive any shocks (no-shock control group).ResultsWhile no significant results of noradrenergic stimulation through yohimbine were obtained using conventional frequentist analyses, additional Bayesian analyses provided strong evidence for the absence of an association between pharmacological treatment and working memory performance. We further observed no effect of controllability and no interaction between noradrenergic stimulation and the manipulation of controllability.ConclusionsOur results suggest that noradrenergic stimulation through yohimbine does not affect (non-spatial) working memory in healthy human participants.

Accounting for stimulus-specific variation in precision reveals a discrete capacity limit in visual working memory.

If we view a visual scene that contains many objects, then momentarily close our eyes, some details persist while others seem to fade. Discrete models of visual working memory (VWM) assume that only a few items can be actively maintained in memory, beyond which pure guessing will emerge. Alternatively, continuous resource models assume that all items in a visual scene can be stored with some precision. Distinguishing between these competing models is challenging, however, as resource models that allow for stochastically variable precision (across items and trials) can produce error distributions that resemble random guessing behavior. Here, we evaluated the hypothesis that a major source of variability in VWM performance arises from systematic variation in precision across the stimuli themselves; such stimulus-specific variability can be incorporated into both discrete-capacity and variable-precision resource models. Participants viewed multiple oriented gratings, and then reported the orientation of a cued grating from memory. When modeling the overall distribution of VWM errors, we found that the variable-precision resource model outperformed the discrete model. However, VWM errors revealed a pronounced "oblique effect," with larger errors for oblique than cardinal orientations. After this source of variability was incorporated into both models, we found that the discrete model provided a better account of VWM errors. Our results demonstrate that variable precision across the stimulus space can lead to an unwarranted advantage for resource models that assume stochastically variable precision. When these deterministic sources are adequately modeled, human working memory performance reveals evidence of a discrete capacity limit. (PsycINFO Database Record

An energy-efficient intrinsic functional organization of human working memory: A resting-state functional connectivity study

Working memory (WM) is the active maintenance of currently relevant information that was just experienced or retrieved from long-term memory but no longer exists in the external environment; however, the intrinsic functional organization of the brain underlying human WM performance remains largely unknown. We hypothesize that the intrinsic functional organization of human WM is an energy-efficient system. We tested this hypothesis by analyzing associations between WM performance (reaction times of correct responses) at different task difficulties (2-back and 3-back tasks) and the resting-state functional connectivity density (FCD) and strength (FCS) in 282 healthy young adults. Voxel-based FCD analysis showed that the reaction times were negatively correlated with the FCD values of several brain regions known to be engaged in WM performance: the right inferior parietal lobule and inferior frontal gyrus for both the 2-back and the 3-back tasks and the right superior parietal lobule, supramarginal gyrus, left inferior parietal lobule and bilateral middle occipital gyrus for the 3-back task. Further analyses showed that the FCS values of these regions with several frontal, parietal and occipital regions were also negatively correlated with the reaction times; the 3-back task was associated with much more functional connections than the 2-back task. These findings suggest that the intrinsic working memory network is an energy-efficient and hierarchical system. A simple working memory task is controlled only by the core subsystem; however, a complex working memory task is associated with more nodes and connections of the system.

Spatial Working Memory in Humans Depends on Theta and High Gamma Synchronization in the Prefrontal Cortex

Previous, albeit correlative, findings have shown thatthe neural mechanisms underlying working memory critically require cross-structural and cross-frequency coupling mechanisms between theta and gamma neural oscillations. However, the direct causality between cross-frequency coupling and working memory performance remains to be demonstrated. Here we externally modulated the interaction of theta and gamma rhythms in the prefrontal cortex using novel cross-frequency protocols of transcranial alternating current stimulation to affect spatial working memory performance in humans. Enhancement of working memory performance and increase of global neocortical connectivity were observed when bursts of high gamma oscillations (80-100Hz) coincided with the peaks of the theta waves, whereas superimposition on the trough of the theta wave and low gamma frequency protocols were ineffective. Thus, our results demonstrate the sensitivity of working memory performance and global neocortical connectivity to the phase and rhythm of the externally driven theta-gamma cross-frequency synchronization.

Gut Taste Stimulants Alter Brain Activity in Areas Related to Working Memory: a Pilot Study

Background/Aims: Taste perception is one of the most important primary oral reinforcers, driving nutrient and energy intake as well as toxin avoidance. Taste receptors in the gastrointestinal tract might as well impact appetitive or aversive behavior and thus influence learning tasks and a close relation of neural taste processing and working memory networks seems plausible. Methods: In the present pilot study, we determined the effects of five taste qualities “bitter” (quinine), “sweet” (glucose), “sour” (citric acid), “salty” (NaCl) and “umami” (monosodium glutamate, MSG) on working memory processing using functional MRI and their effect on plasma insulin and glucose levels. On six separate occasions, subjects received one of the following test substances dissolved in 200 mL tap water via a nasogastric tube (to circumvent the oral cavity): 1) 2g citric acid corresponding to 52 mM, 2) 2g NaCl; 171 mM, 3) 0.017g quinine; 0.26 mM, 4) 1g monosodium glutamate; 30 mM, 5) 25g glucose; 694 mM and 6) 200 mL tap water (placebo). Results: The taste qualities “bitter” and “umami” significantly altered brain activation patterns in the primary gustatory cortex as well as in subcortical structures, previously reported to be involved in emotional learning and memory. In contrast, glucose did not reveal any statistically significant brain activation difference. Working memory performance was not different over the six treatments. Plasma insulin and glucose levels were not affected by the different taste substances (MSG, quinine, NaCl and citric acid). Conclusions: in this pilot trial, we demonstrate that acute intragastric administration of different taste substances does not affect working memory performance in humans. However, “umami” and “bitter” have effects on brain areas involved in neural working memory, overpowering the effects of “sweet”, “salty” and “sour” reception.

Effects of Neuregulin 3 Genotype on Human Prefrontal Cortex Physiology

The neuregulin 3 gene (NRG3) plays pleiotropic roles in neurodevelopment and is a putative susceptibility locus for schizophrenia. Specifically, the T allele of NRG3 rs10748842 has been associated with illness risk, altered cognitive function, and the expression of a novel splice isoform in prefrontal cortex (PFC), but the neural system effects are unexplored. Here, we report an association between rs10748842 and PFC physiology as measured by functional magnetic resonance imaging of human working memory performance, where a convincing link between increased genetic risk for schizophrenia and increased activation in some PFC areas has been established. In 410 control individuals (195 males, 215 females), we detected a highly significant effect of NRG3 genotype manifesting as an unanticipated increase in ventrolateral PFC activation in nonrisk-associated C allele carriers. An additional analysis including 78 patients with schizophrenia spectrum disorders (64 males, 14 females) and 123 unaffected siblings (53 males, 70 females) revealed a whole-brain significant genotype by group interaction in right dorsolateral PFC (DLPFC), manifesting as a relative activation increase in healthy controls and siblings (C > T/T) and as a hypoactivation in patients (T/T > C). These observed genotype-dependent effects in PFC were not explained by task performance and did not conform to established locales of prefrontal inefficiency linked to genetic risk for schizophrenia. Our data indicate a complex modulation of brain physiology by rs10748842, which does not fit the simple inefficiency model of risk association in DLPFC and suggests that other neurobiological mechanisms are involved.

Low-arousal speech noise improves performance in N-back task: an ERP study.

The relationship between noise and human performance is a crucial topic in ergonomic research. However, the brain dynamics of the emotional arousal effects of background noises are still unclear. The current study employed meaningless speech noises in the n-back working memory task to explore the changes of event-related potentials (ERPs) elicited by the noises with low arousal level vs. high arousal level. We found that the memory performance in low arousal condition were improved compared with the silent and the high arousal conditions; participants responded more quickly and had larger P2 and P3 amplitudes in low arousal condition while the performance and ERP components showed no significant difference between high arousal and silent conditions. These findings suggested that the emotional arousal dimension of background noises had a significant influence on human working memory performance, and that this effect was independent of the acoustic characteristics of noises (e.g., intensity) and the meaning of speech materials. The current findings improve our understanding of background noise effects on human performance and lay the ground for the investigation of patients with attention deficits.

Cognitive Functions of the Cerebellum

The cerebellum, the often forgotten “little brain” at the back the cerebrum, has gained significant attention in the last two decades (Desmond, 2010). Although traditionally considered limited in function to component processes of motor control, astute clinicians and researchers posited that such a highly organized brain structure composed of approximately as many neurons as in the cerebrum must have some cognitive function or at least exert some influence on cognitive processes. Despite carefully conducted studies yielding convincing data, papers imputing cognitive function to the cerebellum had been banished to the carousel of rejection. As noted in the paper by Henrietta Leiner, “One peer reviewer actually wrote, ‘This couldn’t possibly be true or we would have discovered it long ago.’” Even current neurology handbooks tend to limit discussion on the outcome of cerebellar pathology to specific motor signs and symptoms. A change in the course of tradition has required a strong theoretical basis, creative neuroanatomy, perceptive clinical observation, rigorous neuropsychological testing, all complemented by human brain imaging. Forward-thinking scientists in each of these areas contributed to this special issue of Neuropsychology Review on cognitive functions of the cerebellum. The five papers are written from different perspectives on the cerebellum, its far-reaching yet systematic connections with supratentorial brain structures, its functions, and the challenges faced in presenting discoveries inconsistent with traditional beliefs. Henrietta Leiner, a mathematician, physicist, computer scientist turned neuroscientist, pioneered new horizons in all areas into which she delved. New voices from dogged thinkers formed a critical impetus for rigorous study to challenge cerebellar doctrine about its functions and also its evolutionary purpose. As noted in the current piece, the Leiners (Henrietta and her late husband, Alan) had put forth the proposition that enlargement of the cerebellum in humans, complemented with development of the massive connections with the supratentorium, occurred in step with the emergence of language. Thus, the cerebellum may have enabled rapid language-based thinking and working memory abilities to support speech perception and production. Jeremy Schmahmann relates his scientific pursuit of cerebellar function through anatomy, neurology, and neuropsychology. His story echoes those of other innovators of new concepts about cerebellar functions, indicating resistance from peers in their ability to break set from the indoctrination of the position that the functions of the cerebellum are solely in the motor domain and cannot contribute to higher-order cognition. Dr. Schmahmann’s systematic analysis of the cerebellum’s functions has led him to delineate a set of general principles of its functions. Included is what he has identified as the Cerebellar Cognitive Affective Syndrome, which has been a cornerstone for current theories about autism and other neurological disorders with an affective component. Andreea Bostan and Peter Strick present an anatomically-based argument that structural interactions between cerebellar and supratentorial structures, including the basal ganglia, provide the communication means for the cerebellum to influence higher-order functions. They review their exquisite tracing studies using rabies virus, which enables identification of multi-synaptic connections traversing extensively across brain systems. The success of these studies has been pivotal in providing incontrovertible evidence for a complex system of closed loop bidirectional communication between selective cerebellar and cortical sites and between selective cerebellar and basal ganglial sites in primates. Cherie Marvel and John Desmond provide replicable support from functional imaging studies on the role of selective regions of the cerebellum in verbal working memory performance in humans. Given the role of the cerebellum as contributing to phonological storage (possibly unique to spoken language) and perhaps even extending working memory capacity, these studies are in keeping with the proposition of the Leiners that the cerebellum, with its great size and high-speed connectivity, with selective regions of the supratentorial brain was essential for human language to evolve. Natalie Zahr, Anne-Lise Pitel, Sandra Chanraud, and I present a focused review on how human neuroimaging studies of chronic alcoholism have furthered our understanding of cerebellar function. The review includes studies using a variety of magnetic resonance imaging (MRI) methods, including structural MRI, diffusion tensor imaging (DTI), fMRI, and MR spectroscopy in conjunction with neuropsychological study. The central tenet is that disruption of an executive frontocerebellar network is a major contributor to characteristic behaviors of alcoholics that, on the one hand, sustain alcohol use disorders possibly through cerebellar conditioning mechanisms, and on the other hand, lead to compensation for frontally-based dysfunctions in alcoholism. As imaging methods improve, we may be in the position to visualize and quantify the integrity of structures in vivo currently hidden within the cerebellum, such as the dentate nucleus (cover figure), in addition to assessing their associated functions. Figure 1 Cover image

Somatosensory working memory performance in humans depends on both engagement and disengagement of regions in a distributed network

Successful working memory (WM) requires the engagement of relevant brain areas but possibly also the disengagement of irrelevant areas. We used magnetoencephalography (MEG) to elucidate the temporal dynamics of areas involved in a somatosensory WM task. We found an increase in gamma band activity in the primary and secondary somatosensory areas during encoding and retention, respectively. This was accompanied by an increase of alpha band activity over task-irrelevant regions including posterior and ipsilateral somatosensory cortex. Importantly, the alpha band increase was strongest during successful WM performance. Furthermore, we found frontal gamma band activity that correlated both with behavioral performance and the alpha band increase. We suggest that somatosensory gamma band activity reflects maintenance and attention-related components of WM operations, whereas alpha band activity reflects frontally controlled disengagement of task-irrelevant regions. Our results demonstrate that resource allocation involving the engagement of task-relevant and disengagement of task-irrelevant regions is needed for optimal task execution.

Transcranial magnetic stimulation (TMS) applied to left dorsolateral prefrontal cortex disrupts verbal working memory performance in humans

Working memory refers to the temporary maintenance and processing of information and involves executive processes that manipulate the contents of the working memory. The role of the executive function in the human left dorsolateral prefrontal cortex (LDLPFC) was explored using transcranial magnetic stimulation (TMS) after confirming the LDLPFC activation using fMRI. We applied double-pulse TMS having a 100-ms inter-pulse interval to LDLPFC immediately after the subjects finished reading the sentences of the reading span test (RST) task, an efficient measure of verbal working memory, in which dual tasks that include both sentence comprehension and word maintenance are required. Using eight normal participants, we found a significant deterioration of performance, i.e., decreased number of correctly reported words, in RST due to TMS stimulation of LDLPFC. Evidence suggests that transient functional disruption of the LDLPFC impairs performance in the maintenance processing of the RST task.

Combined D1/D2 receptor stimulation under conditions of dopamine depletion impairs spatial working memory performance in humans

The mesocortical dopamine system is regarded as an important modulator of working memory. While it has been established that stimulation of the D1/D2 receptor in primates can improve spatial working memory performance, findings in humans are less consistent. Recent studies in humans suggest that global depletion of dopamine via tyrosine/phenylalanine depletion may impair spatial working memory performance, although these results are also inconsistent, and it has been suggested that task differences may partly underlie the inconsistent findings. This study had two aims: (1) to investigate the effects of acute tyrosine depletion (TPD) on a number of working memory tasks and (2) to examine whether stimulation of D1/D2 receptors under conditions of TPD can attenuate or "reverse" TPD-induced working memory impairments. Eighteen healthy male participants performed a spatial working memory delayed-recognition task, non-spatial working memory task and spatial n-back task on three separate occasions, after TPD, TPD and pergolide (D1/D2 agonist), and placebo. TPD did not impair working memory performance on any of the tasks administered. However, stimulation of D1/D2 receptors under TPD conditions caused a subtle impairment in spatial working memory performance. The finding that D1/D2 stimulation under TPD conditions impairs working memory highlights the complexity of functional effects of augmenting dopaminergic transmission within a dopamine-depleted state. The lack of TPD-related effects on a range of working memory tasks questions the reliability of TPD as a modulator of dopamine function and working memory performance in humans.

Frontal and Temporal Dopamine Release during Working Memory and Attention Tasks in Healthy Humans: a Positron Emission Tomography Study Using the High-Affinity Dopamine D2Receptor Ligand [11C]FLB 457

Experimental studies on animals have shown that dopamine is a key neurotransmitter in the regulation of working memory (WM) functions in the prefrontal cortex. In humans, blood flow studies show prefrontal involvement in WM functions, but direct evidence for the involvement of the dopaminergic system in WM is lacking. Using positron emission tomography with a recently developed high-affinity dopamine D2 receptor tracer, [11C]FLB 457, we explored frontal, temporal, and parietal D2 receptor availability in 12 healthy volunteers while they were performing verbal WM and sustained attention tasks. During the performance of both tasks, reduced D2 receptor availability was observed in the left ventral anterior cingulate, suggesting an attention or arousal-related increase in dopamine release during these tasks. Compared with the sustained attention task, the verbal WM task reduced D2 receptor availability in the ventrolateral frontal cortex bilaterally and in the left medial temporal structures (amygdala, hippocampus), suggesting that dopamine release in these regions might have a specific role in WM. In addition, correlation analyses indicated that increased dopamine release in the right ventrolateral frontal cortex and the left ventral anterior cingulate during the WM task was associated with faster and more stable WM performance, respectively. Our results indicate that regionally specific components of the frontotemporal dopaminergic network are functionally involved in WM performance in humans.

The pharmacology of human working memory.

Experimental studies conducted primarily on non-human primates have begun to address the anatomical and neurochemical correlates of working memory. There is an associated growing body of experimental literature investigating whether modulating key neurotransmitters can facilitate working memory in humans. This paper reviews evidence that acute modulation of dopamine in particular, but also noradrenaline, acetylcholine and serotonin may influence working-memory performance in humans. Differences in neurochemical specificity with regard to stages of working memory, type of working memory (spatial or non-spatial) and cortical effects are also discussed. This evidence has contributed to neuropharmacological understanding of working memory in humans. The important therapeutic consequences of a better understanding of facilitation of working memory is discussed in reference to schizophrenia, Parkinson's disease and Alzheimer's disease.