Showing papers on "Working memory published in 2018"

PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders.

Abstract: Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out the contribution of certain neuronal subpopulations in refining cortical representations. However, growing evidence supports a fundamental role of fast-spiking parvalbumin (PV) GABAergic interneurons in regulating pyramidal neuron activity to drive appropriate behavioral responses. Further, their function is heavily diminished in the prefrontal cortex (PFC) in numerous psychiatric diseases, including schizophrenia and autism. Previous research has demonstrated the importance of the optimal balance of excitation and inhibition (E/I) in cortical circuits in maintaining the efficiency of cortical information processing. Although we are still unraveling the mechanisms of information representation in the PFC, the E/I balance seems to be crucial, as pharmacological, chemogenetic and optogenetic approaches for disrupting E/I balance induce impairments in a range of PFC-dependent behaviors. In this review, we will explore two key hypotheses. First, PV interneurons are powerful regulators of E/I balance in the PFC, and help optimize the representation and processing of supramodal information in PFC. Second, diminishing the function of PV interneurons is sufficient to generate an elaborate symptom sequelae corresponding to those observed in a range of psychiatric diseases. Then, using this framework, we will speculate on whether this circuitry could represent a platform for the development of therapeutic interventions in disorders of PFC function.

Posterior parietal cortex represents sensory history and mediates its effects on behaviour

Abstract: A working memory task in rats demonstrates that the posterior parietal cortex is a critical locus for the representation and use of prior stimulus information. Recent sensory experiences, even when irrelevant to the current task at hand, bias memory and perception in humans and monkeys. Carlos Brody and colleagues show that sensory stimulus history also influences the working memory of rats. Silencing the activity of the posterior parietal cortex (PPC), an area previously implicated in working memory, paradoxically improved the rats' performance in a memory and behaviour task—identifying and reporting the loudest of two auditory stimuli. This improvement was due to the selective reduction of the effects of previous sensory stimuli. Electrophysiological recordings showed that PPC neurons carried more information about sensory stimuli of previous trials than about stimuli of the current trial. These findings suggest a role for PPC in maintaining information on recent sensory history. Many models of cognition and of neural computations posit the use and estimation of prior stimulus statistics1,2,3,4: it has long been known that working memory and perception are strongly impacted by previous sensory experience, even when that sensory history is not relevant to the current task at hand. Nevertheless, the neural mechanisms and regions of the brain that are necessary for computing and using such prior experience are unknown. Here we report that the posterior parietal cortex (PPC) is a critical locus for the representation and use of prior stimulus information. We trained rats in an auditory parametric working memory task, and found that they displayed substantial and readily quantifiable behavioural effects of sensory-stimulus history, similar to those observed in humans5,6 and monkeys7. Earlier proposals that the PPC supports working memory8,9 predict that optogenetic silencing of this region would impair behaviour in our working memory task. Contrary to this prediction, we found that silencing the PPC significantly improved performance. Quantitative analyses of behaviour revealed that this improvement was due to the selective reduction of the effects of prior sensory stimuli. Electrophysiological recordings showed that PPC neurons carried far more information about the sensory stimuli of previous trials than about the stimuli of the current trial. Furthermore, for a given rat, the more information about previous trial sensory history in the neural firing rates of the PPC, the greater the behavioural effect of sensory history, suggesting a tight link between behaviour and PPC representations of stimulus history. Our results indicate that the PPC is a central component in the processing of sensory-stimulus history, and could enable further neurobiological investigation of long-standing questions regarding how perception and working memory are affected by prior sensory information.

Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and predicts future working memory in offspring.

Abstract: Several lines of evidence support the link between maternal inflammation during pregnancy and increased likelihood of neurodevelopmental and psychiatric disorders in offspring. This longitudinal study seeks to advance understanding regarding implications of systemic maternal inflammation during pregnancy, indexed by plasma interleukin-6 (IL-6) concentrations, for large-scale brain system development and emerging executive function skills in offspring. We assessed maternal IL-6 during pregnancy, functional magnetic resonance imaging acquired in neonates, and working memory (an important component of executive function) at 2 years of age. Functional connectivity within and between multiple neonatal brain networks can be modeled to estimate maternal IL-6 concentrations during pregnancy. Brain regions heavily weighted in these models overlap substantially with those supporting working memory in a large meta-analysis. Maternal IL-6 also directly accounts for a portion of the variance of working memory at 2 years of age. Findings highlight the association of maternal inflammation during pregnancy with the developing functional architecture of the brain and emerging executive function.

Working Memory From the Psychological and Neurosciences Perspectives: A Review.

Abstract: Since the concept of working memory was introduced over 50 years ago, different schools of thought have offered different definitions for working memory based on the various cognitive domains that it encompasses. The general consensus regarding working memory supports the idea that working memory is extensively involved in goal-directed behaviors in which information must be retained and manipulated to ensure successful task execution. Before the emergence of other competing models, the concept of working memory was described by the multicomponent working memory model proposed by Baddeley and Hitch. In the present article, the authors provide an overview of several working memory-relevant studies in order to harmonize the findings of working memory from the neurosciences and psychological standpoints, especially after citing evidence from past studies of healthy, aging, diseased, and/or lesioned brains. In particular, the theoretical framework behind working memory, in which the related domains that are considered to play a part in different frameworks (such as memory’s capacity limit and temporary storage) are presented and discussed. From the neuroscience perspective, it has been established that working memory activates the fronto-parietal brain regions, including the prefrontal, cingulate, and parietal cortices. Recent studies have subsequently implicated the roles of subcortical regions (such as the midbrain and cerebellum) in working memory. Aging also appears to have modulatory effects on working memory; age interactions with emotion, caffeine and hormones appear to affect working memory performances at the neurobiological level. Moreover, working memory deficits are apparent in older individuals, who are susceptible to cognitive deterioration. Another younger population with working memory impairment consists of those with mental, developmental, and/or neurological disorders such as major depressive disorder and others. A less coherent and organized neural pattern has been consistently reported in these disadvantaged groups. Working memory of patients with traumatic brain injury was similarly affected and shown to have unusual neural activity (hyper- or hypoactivation) as a general observation. Decoding the underlying neural mechanisms of working memory helps support the current theoretical understandings concerning working memory, and at the same time provides insights into rehabilitation programs that target working memory impairments from neurophysiological or psychological aspects.

Persistent Spiking Activity Underlies Working Memory.

Abstract: Persistent activity generated in the PFC during the delay period of working memory tasks represents information about stimuli held in memory and determines working memory performance. Alternative models of working memory, depending on the rhythmicity of discharges or exclusively on short-term synaptic plasticity, are inconsistent with the neurophysiological data.Dual Perspectives Companion Paper:Working Memory: Delay Activity, Yes! Persistent Activity? Maybe Not, by Mikael Lundqvist, Pawel Herman, and Earl K. Miller.

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation.

Abstract: This review focuses on the cognitive neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) based on functional magnetic resonance imaging (fMRI) studies and on recent clinically relevant applications such as fMRI-based diagnostic classification or neuromodulation therapies targeting fMRI deficits with neurofeedback (NF) or brain stimulation. Meta-analyses of fMRI studies of executive functions (EFs) show that ADHD patients have cognitive-domain dissociated complex multisystem impairments in several right and left hemispheric dorsal, ventral and medial fronto-cingulo-striato-thalamic and fronto-parieto-cerebellar networks that mediate cognitive control, attention, timing and working memory (WM). There is furthermore emerging evidence for abnormalities in orbital and ventromedial prefrontal and limbic areas that mediate motivation and emotion control. In addition, poor deactivation of the default mode network (DMN) suggests an abnormal interrelationship between hypo-engaged task-positive and poorly "switched off" hyper-engaged task-negative networks, both of which are related to impaired cognition. Translational cognitive neuroscience in ADHD is still in its infancy. Pattern recognition analyses have attempted to provide diagnostic classification of ADHD using fMRI data with respectable classification accuracies of over 80%. Necessary replication studies, however, are still outstanding. Brain stimulation has been tested in heterogeneously designed, small numbered proof of concept studies targeting key frontal functional impairments in ADHD. Transcranial direct current stimulation (tDCS) appears to be promising to improve ADHD symptoms and cognitive functions based on some studies, but larger clinical trials of repeated stimulation with and without cognitive training are needed to test clinical efficacy and potential costs on non-targeted functions. Only three studies have piloted NF of fMRI-based frontal dysfunctions in ADHD using fMRI or near-infrared spectroscopy, with the two larger ones finding some improvements in cognition and symptoms, which, however, were not superior to the active control conditions, suggesting potential placebo effects. Neurotherapeutics seems attractive for ADHD due to their safety and potential longer-term neuroplastic effects, which drugs cannot offer. However, they need to be thoroughly tested for short- and longer-term clinical and cognitive efficacy and their potential for individualized treatment.

Gamma and beta bursts during working memory readout suggest roles in its volitional control

Abstract: Working memory (WM) activity is not as stationary or sustained as previously thought. There are brief bursts of gamma (~50–120 Hz) and beta (~20–35 Hz) oscillations, the former linked to stimulus information in spiking. We examined these dynamics in relation to readout and control mechanisms of WM. Monkeys held sequences of two objects in WM to match to subsequent sequences. Changes in beta and gamma bursting suggested their distinct roles. In anticipation of having to use an object for the match decision, there was an increase in gamma and spiking information about that object and reduced beta bursting. This readout signal was only seen before relevant test objects, and was related to premotor activity. When the objects were no longer needed, beta increased and gamma decreased together with object spiking information. Deviations from these dynamics predicted behavioral errors. Thus, beta could regulate gamma and the information in WM. Previously, the authors have shown that working memory can be maintained by brief gamma oscillation bursts. Here, the authors use a new task to further demonstrate the dynamics of gamma and beta oscillations in working memory readout, independent of behavioral response.

Working Memory: Delay Activity, Yes! Persistent Activity? Maybe Not

Abstract: Persistent spiking has been thought to underlie working memory (WM). However, virtually all of the evidence for this comes from studies that averaged spiking across time and across trials, which masks the details. On single trials, activity often occurs in sparse transient bursts. This has important computational and functional advantages. In addition, examination of more complex tasks reveals neural coding in WM is dynamic over the course of a trial. All this suggests that spiking is important for WM, but that its role is more complex than simply persistent spiking.Dual Perspectives Companion Paper:Persistent Spiking Activity Underlies Working Memory, by Christos Constantinidis, Shintaro Funahashi, Daeyeol Lee, John D. Murray, Xue-Lian Qi, Min Wang, and Amy F.T. Arnsten.

Working Memory and Executive Attention: A Revisit:

Abstract: In this follow-up to my 2002 article on working memory capacity, fluid intelligence, and executive attention in Current Directions in Psychological Science, I review even more evidence supporting the idea that the ability to control one’s attention (i.e., executive attention) is important to working memory and fluid intelligence. I now argue that working memory tasks reflect primarily the maintenance of information, whereas fluid intelligence tests reflect primarily the ability to disengage from recently attended and no longer useful information. I also point out some conclusions in the 2002 article that now appear to be wrong.

Dissociable Decoding of Spatial Attention and Working Memory from EEG Oscillations and Sustained Potentials.

Abstract: In human scalp EEG recordings, both sustained potentials and alpha-band oscillations are present during the delay period of working memory tasks and may therefore reflect the representation of information in working memory. However, these signals may instead reflect support mechanisms rather than the actual contents of memory. In particular, alpha-band oscillations have been tightly tied to spatial attention and may not reflect location-independent memory representations per se. To determine how sustained and oscillating EEG signals are related to attention and working memory, we attempted to decode which of 16 orientations was being held in working memory by human observers (both women and men). We found that sustained EEG activity could be used to decode the remembered orientation of a stimulus, even when the orientation of the stimulus varied independently of its location. Alpha-band oscillations also carried clear information about the location of the stimulus, but they provided little or no information about orientation independently of location. Thus, sustained potentials contain information about the object properties being maintained in working memory, consistent with previous evidence of a tight link between these potentials and working memory capacity. In contrast, alpha-band oscillations primarily carry location information, consistent with their link to spatial attention.SIGNIFICANCE STATEMENT Working memory plays a key role in cognition, and working memory is impaired in several neurological and psychiatric disorders. Previous research has suggested that human scalp EEG recordings contain signals that reflect the neural representation of information in working memory. However, to conclude that a neural signal actually represents the object being remembered, it is necessary to show that the signal contains fine-grained information about that object. Here, we show that sustained voltages in human EEG recordings contain fine-grained information about the orientation of an object being held in memory, consistent with a memory storage signal.

The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies as a Function of Age and is Associated with Changes in Episodic Memory and Processing Speed

Abstract: The default mode network (DMN) supports memory functioning and may be sensitive to preclinical Alzheimer's pathology. Little is known, however, about the longitudinal trajectory of this network's intrinsic functional connectivity (FC). In this study, we evaluated longitudinal FC in 111 cognitively normal older human adults (ages 49-87, 46 women/65 men), 92 of whom had at least three task-free fMRI scans (n = 353 total scans). Whole-brain FC and three DMN subnetworks were assessed: (1) within-DMN, (2) between anterior and posterior DMN, and (3) between medial temporal lobe network and posterior DMN. Linear mixed-effects models demonstrated significant baseline age × time interactions, indicating a nonlinear trajectory. There was a trend toward increasing FC between ages 50-66 and significantly accelerating declines after age 74. A similar interaction was observed for whole-brain FC. APOE status did not predict baseline connectivity or change in connectivity. After adjusting for network volume, changes in within-DMN connectivity were specifically associated with changes in episodic memory and processing speed but not working memory or executive functions. The relationship with processing speed was attenuated after covarying for white matter hyperintensities (WMH) and whole-brain FC, whereas within-DMN connectivity remained associated with memory above and beyond WMH and whole-brain FC. Whole-brain and DMN FC exhibit a nonlinear trajectory, with more rapid declines in older age and possibly increases in connectivity early in the aging process. Within-DMN connectivity is a marker of episodic memory performance even among cognitively healthy older adults.SIGNIFICANCE STATEMENT Default mode network and whole-brain connectivity, measured using task-free fMRI, changed nonlinearly as a function of age, with some suggestion of early increases in connectivity. For the first time, longitudinal changes in DMN connectivity were shown to correlate with changes in episodic memory, whereas volume changes in relevant brain regions did not. This relationship was not accounted for by white matter hyperintensities or mean whole-brain connectivity. Functional connectivity may be an early biomarker of changes in aging but should be used with caution given its nonmonotonic nature, which could complicate interpretation. Future studies investigating longitudinal network changes should consider whole-brain changes in connectivity.

Dance Training Is Superior to Repetitive Physical Exercise in Inducing Brain Plasticity in the Elderly

Abstract: Animal research indicates that a combination of physical activity and sensory enrichment has the largest and the only sustaining effect on adult neuroplasticity. Dancing has been suggested as a human homologue to this combined intervention as it poses demands on both physical and cognitive functions. For the present exploratory study, we designed an especially challenging dance program in which our elderly participants constantly had to learn novel and increasingly difficult choreographies. This six-month-long program was compared to conventional fitness training matched for intensity. An extensive pre/post-assessment was performed on the 38 participants (63–80 y), covering general cognition, attention, memory, postural and cardio-respiratory performance, neurotrophic factors and–most crucially–structural MRI using an exploratory analysis. For analysis of MRI data, a new method of voxel-based morphometry (VBM) designed specifically for pairwise longitudinal group comparisons was employed. Both interventions increased physical fitness to the same extent. Pronounced differences were seen in the effects on brain volumes: Dancing compared to conventional fitness activity led to larger volume increases in more brain areas, including the cingulate cortex, insula, corpus callosum and sensorimotor cortex. Only dancing was associated with an increase in plasma BDNF levels. Regarding cognition, both groups improved in attention and spatial memory, but no significant group differences emerged. The latter finding may indicate that cognitive benefits may develop later and after structural brain changes have taken place. The present results recommend our challenging dance program as an effective measure to counteract detrimental effects of aging on the brain.

Cortical specialization for attended versus unattended working memory.

Abstract: Items held in working memory can be either attended or not, depending on their current behavioral relevance. It has been suggested that unattended contents might be solely retained in an activity-silent form. Instead, we demonstrate here that encoding unattended contents involves a division of labor. While visual cortex only maintains attended items, intraparietal areas and the frontal eye fields represent both attended and unattended items.

A Hierarchical Model of Inhibitory Control

Abstract: Inhibitory control describes the suppression of goal-irrelevant stimuli and behavioral responses. Current developmental taxonomies distinguish between Response Inhibition - the ability to suppress a prepotent motor response, and Attentional Inhibition - the ability to resist interference from distracting stimuli. Response Inhibition and Attentional Inhibition have exhibited moderately strong positive correlations in previous studies, suggesting they are closely related cognitive abilities. These results may reflect the use of cognitive tasks combining Stimulus-Stimulus- and Stimulus-Response-conflict as indicators of both constructs, which may have conflated their empirical association. Additionally, previous statistical modeling studies have not controlled for individual differences in Working Memory Capacity, which may account for some of the empirical overlap between Response Inhibition and Attentional Inhibition. The aim of the current study was to test a hierarchical model of inhibitory control that specifies Working Memory Capacity as a higher-order cognitive construct. Response Inhibition and Attentional Inhibition were conceptualized as lower-order cognitive mechanisms that should be empirically independent constructs apart from their shared reliance on Working Memory Capacity for active maintenance of goal-relevant representations. Measures of performance on modified stimulus-response compatibility tasks, complex memory span, and non-selective stopping tasks were obtained from 136 preadolescent children (M = 11 years, 10 months, SD = 8 months). Consistent with hypotheses, results from Structural Equation Modeling demonstrated that the Response Inhibition and Attentional Inhibition factors were empirically independent constructs that exhibited partial statistical dependence on the Working Memory Capacity factor. These findings have important implications for current theories and models of inhibitory control during development.

Multilayer network switching rate predicts brain performance.

Abstract: Large-scale brain dynamics are characterized by repeating spatiotemporal connectivity patterns that reflect a range of putative different brain states that underlie the dynamic repertoire of brain functions. The role of transition between brain networks is poorly understood, and whether switching between these states is important for behavior has been little studied. Our aim was to model switching between functional brain networks using multilayer network methods and test for associations between model parameters and behavioral measures. We calculated time-resolved fMRI connectivity in 1,003 healthy human adults from the Human Connectome Project. The time-resolved fMRI connectivity data were used to generate a spatiotemporal multilayer modularity model enabling us to quantify network switching, which we define as the rate at which each brain region transits between different networks. We found (i) an inverse relationship between network switching and connectivity dynamics, where the latter was defined in terms of time-resolved fMRI connections with variance in time that significantly exceeded phase-randomized surrogate data; (ii) brain connectivity was lower during intervals of network switching; (iii) brain areas with frequent network switching had greater temporal complexity; (iv) brain areas with high network switching were located in association cortices; and (v) using cross-validated elastic net regression, network switching predicted intersubject variation in working memory performance, planning/reasoning, and amount of sleep. Our findings shed light on the importance of brain dynamics predicting task performance and amount of sleep. The ability to switch between network configurations thus appears to be a fundamental feature of optimal brain function.

Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall

Abstract: Objective. We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient's own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval. Approach. We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model of hippocampal CA3 and CA1 neural firing is computed that predicts activation patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results. MIMO model-derived electrical stimulation delivered to the same CA1 locations during the sample phase of DMS trials facilitated short-term/working memory by 37% during the task. Longer term memory retention was also tested in the same human subjects with a delayed recognition (DR) task that utilized images from the DMS task, along with images that were not from the task. Across the subjects, the stimulated trials exhibited significant improvement (35%) in both short-term and long-term retention of visual information. Significance. These results demonstrate the facilitation of memory encoding which is an important feature for the construction of an implantable neural prosthetic to improve human memory.

A meta-analysis of the effects of antidepressants on cognitive functioning in depressed and non-depressed samples

Abstract: A thorough understanding of the cognitive effects of antidepressant medications is essential given their frequency of use. This meta-analysis was conducted to investigate whether antidepressants differentially affect the various domains of cognitive functioning for depressed and non-depressed participants. An electronic search of PsycInfo, Medline and Google Scholar was conducted for all journal articles published between January 1998 and January 2017. Thirty-three studies were included enabling calculation of Hedges' g using a random effects model for the cognitive domains of divided attention, executive function, expressive language, immediate memory, perceptual motor skills, processing speed, recent memory, sustained attention, visuospatial-constructional skills and working memory. Results revealed that overall, antidepressants have a modest, positive effect on divided attention, executive function, immediate memory, processing speed, recent memory and sustained attention for depressed participants. Selective serotonin reuptake inhibitors (SSRI's) were found to have the greatest positive effect on cognition for depressed participants, as compared to the other classes of antidepressants analysed. Antidepressants did not significantly affect cognitive function in non-depressed participants.

Cognitive and Affective Perspective-Taking: Evidence for Shared and Dissociable Anatomical Substrates.

Abstract: Perspective-taking refers to the ability to recognize another person's point of view. Crucial to the development of interpersonal relationships and prosocial behavior, perspective-taking is closely linked to human empathy, and like empathy, perspective-taking is commonly subdivided into cognitive and affective components. While the two components of empathy have been frequently compared, the differences between cognitive and affective perspective-taking have been under-investigated in the cognitive neuroscience literature to date. Here, we define cognitive perspective-taking as the ability to infer an agent's thoughts or beliefs, and affective perspective-taking as the ability to infer an agent's feelings or emotions. In this paper, we review data from functional imaging studies in healthy adults as well as behavioral and structural imaging studies in patients with behavioral variant frontotemporal dementia in order to determine if there are distinct neural correlates for cognitive and affective perspective-taking. Data suggest that there are both shared and non-shared cognitive and anatomic substrates. For example, while both types of perspective-taking engage regions such as the temporoparietal junction, precuneus, and temporal poles, only affective perspective-taking engages regions within the limbic system and basal ganglia. Differences are also observed in prefrontal cortex: while affective perspective-taking engages ventromedial prefrontal cortex, cognitive perspective-taking engages dorsomedial prefrontal cortex and dorsolateral prefrontal cortex (DLPFC). To corroborate these findings, we also examine if cognitive and affective perspective-taking share the same relationship with executive functions. While it is clear that affective perspective-taking requires emotional substrates that are less prominent in cognitive perspective-taking, it remains unknown to what extent executive functions (including working memory, mental set switching, and inhibitory control) may contribute to each process. Overall results indicate that cognitive perspective-taking is dependent on executive functioning (particularly mental set switching), while affective perspective-taking is less so. We conclude with a critique of the current literature, with a focus on the different outcome measures used across studies and misconceptions due to imprecise terminology, as well as recommendations for future research.

Digital biomarkers of cognitive function

Abstract: To identify digital biomarkers associated with cognitive function, we analyzed human–computer interaction from 7 days of smartphone use in 27 subjects (ages 18–34) who received a gold standard neuropsychological assessment. For several neuropsychological constructs (working memory, memory, executive function, language, and intelligence), we found a family of digital biomarkers that predicted test scores with high correlations (p < 10−4). These preliminary results suggest that passive measures from smartphone use could be a continuous ecological surrogate for laboratory-based neuropsychological assessment.

Reconciling persistent and dynamic hypotheses of working memory coding in prefrontal cortex

Abstract: Competing accounts propose that working memory (WM) is subserved either by persistent activity in single neurons or by dynamic (time-varying) activity across a neural population. Here, we compare these hypotheses across four regions of prefrontal cortex (PFC) in an oculomotor-delayed-response task, where an intervening cue indicated the reward available for a correct saccade. WM representations were strongest in ventrolateral PFC neurons with higher intrinsic temporal stability (time-constant). At the population-level, although a stable mnemonic state was reached during the delay, this tuning geometry was reversed relative to cue-period selectivity, and was disrupted by the reward cue. Single-neuron analysis revealed many neurons switched to coding reward, rather than maintaining task-relevant spatial selectivity until saccade. These results imply WM is fulfilled by dynamic, population-level activity within high time-constant neurons. Rather than persistent activity supporting stable mnemonic representations that bridge subsequent salient stimuli, PFC neurons may stabilise a dynamic population-level process supporting WM.