Sternberg Working Memory Task Research Articles

Dataset of human-single neuron activity during a Sternberg working memory task

We present a dataset of 1809 single neurons recorded from the human medial temporal lobe (amygdala and hippocampus) and medial frontal lobe (anterior cingulate cortex, pre-supplementary motor area, ventral medial prefrontal cortex) across 41 sessions from 21 patients that underwent seizure monitoring with depth electrodes. Subjects performed a screening task (907 neurons) to identify images for which highly selective cells were present. Subjects then performed a working memory task (902 neurons), in which they were sequentially presented with 1–3 images for which highly selective cells were present and, following a maintenance period, were asked if the probe was identical to one of the maintained images. This Neurodata Without Borders formatted dataset includes spike times, extracellular spike waveforms, stimuli presented, behavior, electrode locations, and subject demographics. As validation, we replicate previous findings on the selectivity of concept cells and their persistent activity during working memory maintenance. This large dataset of rare human single-neuron recordings and behavior enables the investigation of the neural mechanisms of working memory in humans.

Brain optimization with additional study time: potential brain differences between high- and low-performance college students.

This study investigates potential differences in brain function among high-, average-, and low-performance college students using electroencephalography (EEG). We hypothesize that the increased academic engagement of high-performance students will lead to discernible EEG variations due to the brain's structural plasticity. 61 third-year college students from identical majors were divided into high-performance (n = 20), average-performance (n = 21), and low-performance (n = 20) groups based on their academic achievements. We conducted three EEG experiments: resting state, Sternberg working memory task, and Raven progressive matrix task. Comprehensive analyses of the EEG data from the three experiments focused on power spectral density (PSD) and functional connectivity, with coherence (COH) employed as our primary metric for the latter. The results showed that in all experiments, there were no differences in working memory ability and IQ scores among the groups, and there were no significant differences in the power spectral densities of the delta, theta, alpha1, alpha2, beta, and gamma bands among the groups. Notably, on the Raven test, compared to their high-performing peers, low-performing students showed enhanced functional connectivity in the alpha 1 (8-9 Hz) band that connects the frontal and occipital lobes. We explored three potential explanations for this phenomenon: fatigue, anxiety, and greater cognitive effort required for problem-solving due to inefficient self-regulation and increased susceptibility to distraction. In essence, these insights not only deepen our understanding of the neural basis that anchors academic ability, but also hold promise in guiding interventions that address students' diverse academic needs.

Working Memory Deficit and Attentional Distractibility in Schizophrenia

IntroductionMeta-analyses suggest that patients with schizophrenia show deficit in working memory – both verbal and visual – and are more distractible. Working memory disturbances are even regarded as the central deficit in schizophrenia by some researchers. Theta synchronization (especially over fronto-central areas) is related to cognitive control and executive functioning during working memory encoding and retention.ObjectivesThe main goal of the study was to gain more understanding of the nature of working memory deficit and attentional distractibility in schizophrenia.Methods35 patients with schizophrenia and 39 matched controls were enrolled in our study. Participants performed a modified Sternberg working memory task that contained salient and non-salient distractor items in the retention period. A high-density 128 channel EEG was recorded during the task. Event-related theta (4-7 Hz) synchronization was analyzed during working memory encoding (learning) and retention (distractor filtering) in a later time window (350-550 ms).ResultsPatients with schizophrenia showed weaker working memory performance and increased attentional distractibility compared to the control group: patients had significantly lower hit rates (p < 0.0001) and higher distractor-related commission error rates (p < 0.0001). Theta synchronization was modulated by condition (learning < distractor) in both groups but it was modulated by salience only in controls (salient distractor > non-salient distractor, p[patients] = 0.95, p[controls] < 0.001).ConclusionsOur results suggest that patients with schizophrenia show diminished cognitive control compared to controls in response to salient distractors. Difficulties in cognitive control allocation may contribute to the behavioral results observed in this study.DisclosureNo significant relationships.

Parietal and medial temporal lobe interactions in working memory goal-directed behavior

Working memory is essential for the organization of goal-directed behavior, which involves multiple brain networks. The frontoparietal network has been proposed as a central node for the maintenance and manipulation of information. However, the exact contribution of the frontal and parietal lobes is still unclear as is that of the medial temporal lobe (MTL). Here, we investigated how the frontoparietal network and the MTL coordinate cognitive functions to control working memory in 12 participants, including five men, with medically intractable epilepsy. Participants performed a modified Sternberg working memory task during intracranial electroencephalography recording. The present working memory task was designed to test the different neural states of working memory subprocesses during memory maintenance and operation. First, we observed increased and sustained low-frequency (2–7 Hz) power in the frontal lobe and MTL, relative to baseline activity during the entire working memory task. Parietal alpha (8–13 Hz) power exhibited peak activity during memory operation. Finally, we found a positive correlation in the alpha band between the MTL and the parietal lobe during memory operation. These results indicate that as task demands become specific and goal-directed, the correlation between the MTL and the parietal lobe increases. This finding provides novel insight into the contribution of the MTL-parietal lobe network to voluntary control of working memory.

Latent brain state dynamics and cognitive flexibility in older adults.

Cognitive impairment in older adults is a rapidly growing public health concern as the elderly population dramatically grows worldwide. While it is generally assumed that cognitive deficits in older adults are associated with reduced brain flexibility, quantitative evidence has been lacking. Here, we investigate brain flexibility in healthy older adults (ages 60-85) using a novel Bayesian switching dynamical system algorithm and ultrafast temporal resolution (TR = 490 ms) whole-brain fMRI data during performance of a Sternberg working memory task. We identify latent brain states and characterize their dynamic temporal properties, including state transitions, associated with encoding, maintenance, and retrieval. Crucially, we demonstrate that brain inflexibility is associated with slower and more fragmented transitions between latent brain states, and that brain inflexibility mediates the relation between age and cognitive inflexibility. Our study provides a novel neurocomputational framework for investigating latent dynamic circuit processes underlying brain flexibility and cognition in the context of aging.

Brain Correlates of Verbal Working Memory in Children with Hearing Loss: Auditory Experience Matters

Brain Correlates of Verbal Working Memory in Children with Hearing Loss: Auditory Experience Matters

Amount of Hearing Aid Use Impacts Neural Oscillatory Dynamics Underlying Verbal Working Memory Processing for Children With Hearing Loss.

Objectives:Children with hearing loss (CHL) may exhibit spoken language delays and may also experience deficits in other cognitive domains including working memory. Consistent hearing aid use (i.e., more than 10 hours per day) ameliorates these language delays; however, the impact of hearing aid intervention on the neural dynamics serving working memory remains unknown. The objective of this study was to examine the association between the amount of hearing aid use and neural oscillatory activity during verbal working memory processing in children with mild-to-severe hearing loss.Design:Twenty-three CHL between 8 and 15 years-old performed a letter-based Sternberg working memory task during magnetoencephalography (MEG). Guardians also completed a questionnaire describing the participants’ daily hearing aid use. Each participant’s MEG data was coregistered to their structural MRI, epoched, and transformed into the time–frequency domain using complex demodulation. Significant oscillatory responses corresponding to working memory encoding and maintenance were independently imaged using beamforming. Finally, these whole-brain source images were correlated with the total number of hours of weekly hearing aid use, controlling for degree of hearing loss.Results:During the encoding period, hearing aid use negatively correlated with alpha-beta oscillatory activity in the bilateral occipital cortices and right precentral gyrus. In the occipital cortices, this relationship suggested that with greater hearing aid use, there was a larger suppression of occipital activity (i.e., more negative relative to baseline). In the precentral gyrus, greater hearing aid use was related to less synchronous activity (i.e., less positive relative to baseline). During the maintenance period, hearing aid use significantly correlated with alpha activity in the right prefrontal cortex, such that with greater hearing aid use, there was less right prefrontal maintenance-related activity (i.e., less positive relative to baseline).Conclusions:This study is the first to investigate the impact of hearing aid use on the neural dynamics that underlie working memory function. These data show robust relationships between the amount of hearing aid use and phase-specific neural patterns during working memory encoding and maintenance after controlling for degree of hearing loss. Furthermore, our data demonstrate that wearing hearing aids for more than ~8.5 hours/day may serve to normalize these neural patterns. This study also demonstrates the potential for neuroimaging to help determine the locus of variability in outcomes in CHL.

Audiovisual working memory and association with resting-state regional homogeneity

Multisensory processing is a prevalent research issue. However, multisensory working memory research has received inadequate attention. The present study aimed to investigate the behavioral performance of an audiovisual working memory task and its association with resting-state functional magnetic resonance imaging (fMRI) regional homogeneity (ReHo). A total of 128 healthy participants were enrolled in this study. The participants completed a modified Sternberg working memory task using complex auditory and visual objects as materials involved in different encoding conditions, including semantically congruent audiovisual, semantically incongruent audiovisual, and single modality of auditory or visual object encoding. Two subgroups received resting-state fMRI scans according to their behavioral performances. The results showed that the semantically congruent audiovisual object encoding sped up the later unisensory memory recognition in this task. Moreover, the high behavioral performance (response time, RT) group showed increased ReHo in the executive control network (ECN) and decreased ReHo in the default mode network (DMN) and saline network (SN). In addition, resting-state ReHo values in the ECN nodes (e.g., middle frontal gyrus and superior frontal gyrus) was correlated with RT. These findings suggested that semantically congruent audiovisual processing in working memory was superior to unisensory memory recognition and may be involved in the different functional networks such as ECN.

Aerobic Exercise Mediates Neural Inefficiency Among Adolescents At Risk for Suicide.

This study examined the electroencephalograpy (EEG) coherence and working memory performance effects of a 9-week exercise program on a small group of adolescents at high suicide risk. We randomly assigned 26 adolescents at high suicide risk (based on their scores on the Adolescents Mental Health Inventory- AMHI) into equal sized exercise and no-exercise groups. Before and after the 9-week exercise program, all participants performed the Sternberg working memory task, during which we recorded their EEGs, with electrodes placed at F3, F4, C3, C4, P3, P4, T3, T4, O1, and O2 regions (using the International 10-20 system of EEG electrode placement). We measured working memory performance and inter-hemispheric (F3-F4, C3-C4, T3-T4, P3-P4, O1-O2) and intra-hemispheric (F3-C3, F3-T3, F3-P3, F3-O1, F4-C4, F4-T4, F4-P4, F4-O2) EEG coherence as an index of the participants' underlying neural efficiency. While we found no significant group differences in working memory performances, the exercise group, relative to the no-exercise group, exhibited lower inter- and intra-hemispheric EEG coherence while performing the working memory task. These EEG differences may reflect a mediating effect of aerobic exercise on these participants' neural efficiency.

Working memory deficits in patients with idiopathic restless legs syndrome are associated with abnormal theta-band neural synchrony.

Cognitive impairment, particularly prefrontal function, has been reported in patients with restless legs syndrome. However, working memory performance in patients with restless legs syndrome remains uncertain. The present study aimed to examine working memory performance in patients with restless legs syndrome by investigating electroencephalography theta‐band oscillations within task‐relevant brain regions and the synchronization among oscillations during a working memory task. Twelve female idiopathic patients with restless legs syndrome and 12 female healthy controls participated in this study. Nineteen‐channel electroencephalography data were recorded while participants performed a Sternberg working memory task. We analysed event‐related theta‐band activity and interregional theta‐band phase synchrony during the memory retrieval phase. The spatial pattern of theta‐band phase synchrony was quantified using graph theory measures, including the clustering coefficient, characteristic path length, and small‐world propensity. Considerable increases in theta‐band activity and theta‐band phase synchrony were observed at 600–700 ms in controls and at 650–750 ms in restless legs syndrome subjects after the probe item was presented. During this period, induced theta‐band activity showed lower with borderline significance in the restless legs syndrome subjects than in the controls regardless of channel location (F 4,88 = 3.92, p = .06). Theta‐band phase synchrony between the frontal and posterior regions was significantly reduced in the restless legs syndrome subjects. Inefficiency in both global and local networks in the restless legs syndrome subjects was revealed by the decreased small‐world propensity (t 22 = 2.26, p = .03). Small‐world propensity was negatively correlated with restless legs syndrome severity (r = −.65, p = .02). Our findings suggest that patients with restless legs syndrome have multiple deficits in cognitive processes, including attentional allocation, evaluation of incoming stimuli, and memory manipulation of encoded information during a working memory task. Abnormal local theta‐band neural synchrony and global theta‐band neural synchrony may underlie the neurophysiological mechanism of the working memory dysfunction associated with restless legs syndrome.

Electroencephalography-based cortical sources of working memory in the subjects with opioid addiction: A pilot study.

Background & objectives:Working memory impairments in the subjects of opioid addiction may stem from an aberrant cortical activity in the executive areas, and may help in early identification of individuals with addictive tendencies and may also be used as a neurofeedback mechanism in adjunct to the existing therapeutics.Methods:Electrical neuroimaging via 128-channel electroencephalography (EEG) recording was done in 15 male subjects with opioid addiction (29.45±5.6 yr) during the performance of Sternberg Working Memory Task. EEG data were acquired and analyzed for cortical sources during task as compared to resting (baseline) condition.Results:Working memory deficits were manifested as decrease in accuracy percentage in the subjects with opioid addiction, while no significant difference was seen in reaction time, on comparison with laboratory-acquired matched controls. Standardized low-resolution brain electromagnetic tomography (sLORETA)-based EEG source analysis revealed higher cortical activity in the anterior cingulate cortex, inferior, middle and superior temporal gyri, inferior frontal gyrus, superior parietal lobule, inferior parietal lobule and precuneus, whereas significant lower activity was seen in superior and middle frontal gyri, parietal lobule, cingulate cortex and pre- and postcentral gyri when the task was compared to baseline in the subjects with opioid addiction. Further, a negative correlation was seen between the accuracy of task performance and activation ratio for the significant gyri in the subjects with opioid addiction.Interpretation & conclusions:EEG cortical sources revealed the failure of deactivation of default-mode network (DMN) during the task amongst the subjects with opioid addiction. In addition, there was a decrease in the executive function areas in the subjects with opioid addiction. This lack of sufficiently active executive network and persistence of DMN during the task (as compared to baseline) may potentially form the basis of functional impairments in the subjects with opioid addiction.

Salient distractors open the door of perception: alpha desynchronization marks sensory gating in a working memory task

Focusing attention on relevant information while ignoring distracting stimuli is essential to the efficacy of working memory. Alpha- and theta-band oscillations have been linked to the inhibition of anticipated and attentionally avoidable distractors. However, the neurophysiological background of the rejection of task-irrelevant stimuli appearing in the focus of attention is not fully understood. We aimed to examine whether theta and alpha-band oscillations serve as an indicator of successful distractor rejection. Twenty-four students were enrolled in the study. 64-channel EEG was recorded during a modified Sternberg working memory task where weak and strong (salient) distractors were presented during the retention period. Event-related spectral perturbation in the alpha frequency band was significantly modulated by the saliency of the distracting stimuli, while theta oscillation was modulated by the need for cognitive control. Moreover, stronger alpha desynchronization to strong relative to weak distracting stimuli significantly increased the probability of mistakenly identifying the presented distractor as a member of the memory sequence. Therefore, our results suggest that alpha activity reflects the vulnerability of attention to distracting salient stimuli.

Association of Depression With Functional Mobility in Schizophrenia.

BackgroundFunctional immobility can cause functional disability in patients with schizophrenia and has been linked to prognosis and mortality. Although depression might be a barrier for physical activity engagement, scarce data are present on the relationship between depression and functional mobility (FM) in schizophrenia. Thus, we aimed to investigate the associations among FM, depression, and other clinical correlates in individuals with schizophrenia.MethodsFM was evaluated by the pedometer-assessed daily steps and Timed Up-and-Go (TUG) test in the daily-living and clinical settings, respectively. Psychiatric symptoms were assessed using the Beck Depression Inventory, Brief Psychiatric Rating Scale (BPRS), and State-Trait Anxiety Inventory. Cognitive function was evaluated using the Sternberg Working Memory (SWM) Task. Multiple regression analyses were performed to identify predictive factors associated with FM, with adjustment for relevant covariates.ResultsSixty patients were enrolled in this study. Depression was the most consistent explanatory variable for both pedometer (β = −0.34, p = 0.011) and TUG time (β = 0.32, p = 0.018). Additionally, SWM accuracy (β = −0.29, p = 0.018), BPRS-Withdrawal (β = 0.19, p = 0.139), and fasting blood sugar (β = 0.34, p = 0.008) were associated with TUG time. However, psychotic symptoms and anxiety were not associated with pedometer and TUG.ConclusionsWe identified an association between depression and FM after adjusting for other disorder-related correlates in schizophrenia. Since the intervention goal is functional recovery, improving FM by treating depression may have considerable therapeutic value.

Differences in prefrontal cortex activity based on difficulty in a working memory task using near-infrared spectroscopy

The Prefrontal cortex (PFC) has been highly related to executive functions such as working memory (WM). This study assesses the activity of the PFC in performing the Sternberg WM task (ST) with three levels of difficulty (easy, medium and hard) using the near-infrared spectroscopy (fNIRS) technique. Participants were 43 young and healthy right-handed women. Nine WM task blocks were pseudo randomly presented, three for each difficulty task. The results showed that the participant's performance was better in the easy trials than in the medium and hard trials. Performance in the medium trials was also better than in the hard ones. Bonferroni-corrected paired post-hoc t-tests indicated higher oxygenation in medium and hard tasks than in the easy ones for times between 13 and 42 s in the left lateral PFC and in both, medial and lateral, right PFC. Significant differences in Oxygenated hemoglobin (HbO), Total hemoglobin (HbT) and oxygenation (Oxy) changes depending on the Sternberg WM task were found. Unlike previous studies with fNIRS and WM, the current study uses a highly controlled WM task that differentiates between encoding, retention and retrieval phases, comparing different levels of task load.

0332 Effect of Prior Sleep Duration on Distinct Measures of Daytime Cognitive Performance in Late Adolescence

Abstract Introduction A recent longitudinal study of sleep need changes across adolescence reported how prior sleep duration affects daytime sleepiness and vigilant attention in children ages 10-16 years. In a follow-up study, we extend the age range in a new group of participants and add additional performance tests. Here we report year 1 data on the effect of systematically varied time in bed (TIB) on daytime vigilance, working memory, and decision making. Methods Data are for 52 participants aged 15.0-20.4 years (mean±SD: 17.7±1.8 years). Annually, participants keep each of three different TIB schedules: 7h, 8.5h or 10h TIB for 4 consecutive nights. The 4th night is followed by a laboratory day of performance testing. The day includes four 10-minute psychomotor vigilance tests (PVT); a serial position Sternberg working memory task; and an AX continuous performance test with switch (AX-CPTs) measuring cognitive flexibility in decision making. Results PVT performance evaluated by the log of the signal to noise ratio (LSNR) improved monotonically with increasing TIB (p<0.0001). TIB also affected serial position Sternberg task accuracy (p=0.008) but not the probe position effect (p=0.66), indicating that TIB did not affect working memory. TIB also affected AX-CPTs accuracy (p<0.0001), but TIB did not significantly affect decision making and cognitive flexibility measures extracted from this task (all p>0.09). Conclusion The initial data from this longitudinal study on older adolescents confirm what we observed for younger adolescents. Increasing TIB improves daytime vigilance but does not affect working memory. These initial results also do not indicate a TIB related improvement in decision making. Data from the entire three year longitudinal study will allow us to further investigate relations of performance to prior sleep duration and whether these relations change with age. Results from dose-response studies such as these can help guide sleep duration recommendations. Support PHS grant R01 HL116490 supported this work.

Severity of Topiramate-Related Working Memory Impairment Is Modulated by Plasma Concentration and Working Memory Capacity.

Drug side effects that impair cognition can lead to diminished quality of life and discontinuation of therapy. Topiramate is an antiepileptic drug that elicits cognitive deficits more frequently than other antiepileptic drugs, impairing multiple cognitive domains including language, attention, and memory. Although up to 40% of individuals taking topiramate may experience cognitive deficits, we are currently unable to predict which individuals will be most severely affected before administration. The objective of this study was to show the contributions of plasma concentration and working memory capacity in determining the severity of an individual's topiramate-related cognitive impairment. Subjects were enrolled in a double-blind, placebo-controlled crossover study during which they received a single dose of either 100, 150, or 200 mg topiramate. Working memory function was assessed using a modified Sternberg working memory task with 3 memory loads administered 4 hours after dosing. After adjustment for differences in working memory capacity, each 1 μg/mL of topiramate plasma concentration was associated with a 3.6% decrease in accuracy for all memory loads. Placebo effects occurred as a function of working memory capacity, with individuals with high working memory capacity experiencing less severe placebo-related impairment compared with those with low working memory capacity. Our results demonstrate that severity of topiramate-related cognitive deficits occurs as a function of both drug exposure and baseline cognitive function. By identifying patient- and exposure-related characteristics that modulate the severity of cognitive side effects, topiramate dosing strategies may be individually tailored in the future to prevent unwanted cognitive impairment.

Interpreting neural decoding models using grouped model reliance.

Machine learning algorithms are becoming increasingly popular for decoding psychological constructs based on neural data. However, as a step towards bridging the gap between theory-driven cognitive neuroscience and data-driven decoding approaches, there is a need for methods that allow to interpret trained decoding models. The present study demonstrates grouped model reliance as a model-agnostic permutation-based approach to this problem. Grouped model reliance indicates the extent to which a trained model relies on conceptually related groups of variables, such as frequency bands or regions of interest in electroencephalographic (EEG) data. As a case study to demonstrate the method, random forest and support vector machine models were trained on within-participant single-trial EEG data from a Sternberg working memory task. Participants were asked to memorize a sequence of digits (0–9), varying randomly in length between one, four and seven digits, where EEG recordings for working memory load estimation were taken from a 3-second retention interval. The present results confirm previous findings insofar as both random forest and support vector machine models relied on alpha-band activity in most subjects. However, as revealed by further analyses, patterns in frequency and topography varied considerably between individuals, pointing to more pronounced inter-individual differences than previously reported.

Physical performance is more strongly associated with cognition in schizophrenia than psychiatric symptoms

BackgroundAlthough neurocognitive dysfunction and physical performance are known to be impaired in patients with schizophrenia, evidence regarding the relationship between these two domains remains insufficient. Thus, we aimed to investigate the relationship between various physical performance domains and cognitive domains in individuals with schizophrenia, while considering other disorder-related clinical symptoms. MethodsSixty patients with schizophrenia participated in the study. Cardiorespiratory fitness and functional mobility were evaluated using the step test and supine-to-standing (STS) test, respectively. Executive function and working memory were assessed using the Stroop task and Sternberg working memory (SWM) task, respectively. Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory. Multivariate analyses were performed to adjust for relevant covariates and identify predictive factors associated with neurocognition. ResultsMultiple regression analysis revealed that the step test index was most strongly associated with reaction time in the Stroop task (β = 0.434, p = 0.001) and SWM task (β = 0.331, p = 0.026), while STS test time was most strongly associated with accuracy on the Stoop task (β=−0.418, p = 0.001) and SWM task (β=−0.383, p = 0.007). Total cholesterol levels were positively associated with Stroop task accuracy (β=−0.307, p = 0.018) after controlling for other clinical correlates. However, clinical symptoms were not associated with any variables in Stroop or SWM task. ConclusionsThe present findings demonstrate the relationship between physical performance and neurocognition in patients with schizophrenia. Considering that these factors are modifiable, exercise intervention may help to improve cognitive symptoms in patients with schizophrenia, thereby leading to improvements in function and prognosis.

Post-traumatic stress disorder is associated with altered modulation of prefrontal alpha band oscillations during working memory

ObjectiveTo investigate the relationship between the severity of PTSD symptoms, modulation of alpha band oscillations, and behavioral performance in a working memory task. MethodsMagnetoencephalography data were recorded in 35 participants with combat exposure and various degrees of PTSD symptom severity while they performed a modified Sternberg working memory task: briefly presented sets of two or six letters had to be held in memory and participants indicated whether subsequent probe letters were present or absent from these sets. ResultsPTSD scores were positively correlated with the false positive rate in the high memory load condition. Higher rates of false recognition were associated with negative probes that were seen in recent previous trials (negative probe recency effect) or were physically similar with the list letters. The relative alpha band power in the left middle frontal gyrus was negatively correlated with both PTSD scores and false positive rates. ConclusionsReduced task specific modulation of alpha band oscillations in left middle frontal cortex may reflect alterations in the functions of pattern separation and suppression of memory traces for irrelevant or no longer relevant information in PTSD. SignificanceThe lower amplitude of prefrontal alpha band oscillations may represent an important physiological basis for core PTSD symptoms and can provide a target for interventions to augment response to treatment.

Neural correlates of dynamic changes in working memory performance during one night of sleep deprivation.

Total sleep deprivation (TSD) is common in modern society leading to deterioration of multiple aspects of cognition. Dynamic interaction effect of circadian rhythmicity and homeostatic sleep pressure on sustained attention have been intensively investigated, while how this effect was represented on performance and cerebral responses to working memory, another important element of many neurobehavioral tasks, was not well elucidated. Thirty-six healthy subjects with intermediate chronotype performed the Sternberg working-memory task (SWMT) while undergoing functional magnetic resonance imaging every 2 hr from 10:00 p.m. on the first day to 6:00 a.m. on the second day. Using data from three imaging sessions (10:00 p.m., 04:00 a.m., and 06:00 a.m.), we found that the slowest SWMT reaction time and weakest cerebral responses were not at the end of TSD (06:00 a.m.) but during the early morning (04:00 a.m.) hours of the TSD. In addition, during this worst period of TSD, reaction time for the SWMT were found to be negatively correlated with task-related activation in the angular gyrus and positively correlated with the degree of negative correlation between the control and default networks. Our results revealed a rebound of SWMT reaction time and cerebral responses after the mid-time point of regular biological sleep night and provided more evidence that different cognitive tasks are differentially affected by sleep loss and circadian rhythmicity.