Decreased brain activation during a working memory task at rested baseline is associated with vulnerability to sleep deprivation

STUDY OBJECTIVE: To examine whether differences in patterns of brain activation under baseline conditions relate to the differences in sleep-deprivation vulnerability. DESIGN: Using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging, we scanned 33 healthy young men while they performed the Sternberg working memory task following a normal night of sleep and again following 30 hours of sleep deprivation. From this initial group, based on their Sternberg working memory task performance, we found 10 subjects resilient to sleep deprivation (sleep deprivation-resilient group) and then selected 10 age- and education-matched subjects vulnerable to sleep deprivation (sleep deprivation-vulnerable group). SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Data from 10 young men (mean age 27.8 +/- 1.7 years) in the sleep deprivation-resilient group and 10 young men (mean age 28.2 +/- 1.9 years) in the sleep deprivation-vulnerable group were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared functional magnetic resonance imaging BOLD signal at rested baseline and sleep deprivation states in the 2 groups. As hypothesized, following sleep deprivation, both groups showed significant decreases in global brain activation compared to their rested group baseline. At rested baseline and in the sleep-deprivation state, the sleep deprivation-resilient group had significantly more brain activation than did the sleep deprivation-vulnerable group. There were also differences in functional circuits within and between groups in response to sleep deprivation. CONCLUSIONS: These preliminary data suggest that patterns of brain activation during the Sternberg working memory task at the rested baseline and the sleep-deprivation state, differ across individuals as a function of their sleep-deprivation vulnerability.     

Increasing task difficulty facilitates the cerebral compensatory response to total sleep deprivation

STUDY OBJECTIVES: To test the role of task difficulty in the cerebral compensatory response after total sleep deprivation (TSD). DESIGN: Subjects performed a modified version of Baddeley's logical reasoning task while undergoing functional magnetic resonance imaging twice: once after normal sleep and once following 35 hours of TSD. The task was modified to parametrically manipulate task difficulty. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: 16 young adults (7 women; mean age, 27.6 +/- 6.1 years; education, 15.4 +/- 1.8 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Behaviorally, subjects performed the same after TSD as while well rested. Neuroimaging data revealed a linear increase in cerebral response with a linear increase in task demands in several brain regions after normal sleep. Even stronger linear responses were found after TSD in several brain regions, including bilateral inferior parietal lobes, bilateral temporal cortex, and left inferior and dorsolateral prefrontal cortex. CONCLUSIONS: Task difficulty facilitates the cerebral compensatory response observed following TSD. Compensation manifests as both new regions that did not show significant responses to task demands in the well-rested condition, as well as stronger responses within regions typically underlying task performance. The possible significance of these 2 types of responses should be explored further, as should the importance of the parietal lobes for cognitive performance after TSD.     

Neural correlates of enhanced working-memory performance in dissociative disorder: a functional MRI study

BACKGROUND: Memory functioning has been highlighted as a central issue in pathological dissociation. In non-pathological dissociation, evidence for enhanced working memory has been found, together with greater task-load related activity. So far, no imaging studies have investigated working memory in dissociative patients. METHOD: To assess working memory in dissociative patients functional magnetic resonance imaging was used during performance of a parametric, verbal working-memory task in patients with a dissociative disorder (n=16) and healthy controls (n=16). RESULTS: Imaging data showed that both groups activated brain regions typically involved in working memory, i.e. anterior, dorsolateral and ventrolateral prefrontal cortex (PFC), and parietal cortex. Dissociative patients showed more activation in these areas, particularly in the left anterior PFC, dorsolateral PFC and parietal cortex. In line with these findings, patients made fewer errors with increasing task load compared to controls, despite the fact that they felt more anxious and less concentrated during task performance. CONCLUSIONS: These results extend findings in non-pathological high dissociative individuals, suggesting that trait dissociation is associated with enhanced working-memory capacities. This may distinguish dissociative patients from patients with post-traumatic stress disorder, who are generally characterized by impaired working memory.     

Sleep-dependent motor memory plasticity in the human brain

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.     

Modafinil activates cortical and subcortical sites in the sleep-deprived state

SUBJECT OBJECTIVES: To assess the effect of the wake-promoting drug modafinil on working memory and brain activation in the executive network, following a single night of sleep deprivation. DESIGN: Randomized, placebo-controlled, 4-arm, double-blind evaluation of a single 200-mg dose of modafinil on working memory (1-, 2-, and 3-back)-related functional brain activation and performance following overnight sleep deprivation. SETTING: General Clinical Research Center, Biomedical Imaging Center. SUBJECTS: Eight medication-free men, aged 21 to 35 years. Interventions: Overnight sleep deprivation, single-dose 200-mg modafinil, functional magnetic resonance imaging MEASUREMENTS AND RESULTS: Brain activation patterns and regional signal intensity based on the blood-oxygen level-dependent signal were assessed. The following reaction times were used as measures of performance: (1) attention in the scanner before functional scanning, (2) "back" responses during the active-task block, and (3) attention during the baseline task block. Contrast of activation maps among conditions revealed sleep-deprivation and drug effects, and their interactions. Performance in the deprived state was enhanced by modafinil only at an intermediate (2-back) level of task difficulty and was associated with the recruitment of increased cortical activation volumes. Strong and consistent individual differences in performance were noted on the working memory tasks. CONCLUSIONS: Modafinil effectively counters the adverse effects of overnight sleep deprivation on working memory but only when task difficulty is moderate, recruiting extensive areas in the executive network to do so. Interindividual differences in working-memory performance are stable trait characteristics.     

Increased cerebral response during a divided attention task following sleep deprivation

We recently reported that the brain showed greater responsiveness to some cognitive demands following total sleep deprivation (TSD). Specifically, verbal learning led to increased cerebral activation following TSD while arithmetic resulted in decreased activation. Here we report data from a divided attention task that combined verbal learning and arithmetic. Thirteen normal control subjects performed the task while undergoing functional magnetic resonance imaging (FMRI) scans after a normal night of sleep and following 35 h TSD. Behaviourally, subjects showed only modest impairments following TSD. With respect to cerebral activation, the results showed (a) increased activation in the prefrontal cortex and parietal lobes, particularly in the right hemisphere, following TSD, (b) activation in left inferior frontal gyrus correlated with increased subjective sleepiness after TSD, and (c) activation in bilateral parietal lobes correlated with the extent of intact memory performance after TSD. Many of the brain regions showing a greater response after TSD compared with normal sleep are thought to be involved in control of attention. These data imply that the divided attention task required more attentional resources (specifically, performance monitoring and sustained attention) following TSD than after normal sleep. Other neuroimaging results may relate to the verbal learning and/or arithmetic demands of the task. This is the first study to examine divided attention performance after TSD with neuroimaging and supports our previous suggestion that the brain may be more plastic during cognitive performance following TSD than previously thought.     

Are individual differences in fatigue vulnerability related to baseline differences in cortical activation?

Recent evidence suggests that underlying patterns of cortical activation may partially account for individual differences in susceptibility to the effects of sleep deprivation. Here, functional magnetic resonance imaging (fMRI) was used to examine the activation of military pilots whose sleep-deprivation vulnerability previously was quantified. A Sternberg Working Memory Task (SWMT; S. Sternberg, 1966) was completed alternately with a control task during a 13-min blood oxygen level-dependent fMRI scan. Examination of the activated voxels in response to SWMT indicated that, as a group, the pilots were more similar to fatigue-resistant nonpilots than to fatigue-vulnerable nonpilots. Within the pilots, cortical activation was significantly related to fatigue vulnerability on simulator-flight performance. These preliminary data suggest that baseline fMRI scan activation during a working memory task may correlate with fatigue susceptibility.     

Prefrontal and parietal contributions to spatial working memory

Functional neuroimaging studies consistently implicate a widespread network of human cortical brain areas that together support spatial working memory. This review summarizes our recent functional magnetic resonance imaging studies of humans performing delayed-saccades. These studies have isolated persistent activity in dorsal prefrontal regions, like the frontal eye fields, and the posterior parietal cortex during the maintenance of positional information. We aim to gain insight into the type of information coded by this activity. By manipulating the sensory and motor demands of the working memory task, we have been able to modulate the frontal eye fields and posterior parietal cortex delay-period activity. These findings are discussed in the context of other neurophysiological and lesion-based data and some hypotheses regarding the differential contributions of frontal and parietal areas to spatial working memory are offered. Namely, retrospective sensory coding of space may be more prominent in the posterior parietal cortex, while prospective motor coding of space may be more prominent in the frontal eye fields.     

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.     

The functional neuroanatomy of working memory: contributions of human brain lesion studies

Studies of patients with focal brain lesions remain critical components of research programs attempting to understand human brain function. Whereas functional imaging typically reveals activity in distributed brain regions that are involved in a task, lesion studies can define which of these brain regions are necessary for a cognitive process. Further, lesion studies are less critical regarding the selection of baseline conditions needed in functional brain imaging research. Lesion studies suggest a functional subdivision of the visuospatial sketchpad of working memory with a ventral stream reaching from occipital to temporal cortex supporting object recognition and a dorsal stream connecting the occipital with parietal cortex enabling spatial operations. The phonological loop can be divided into a phonological short-term store in inferior parietal cortex and an articulatory subvocal rehearsal process relying on brain areas necessary for speech production, i.e. Broca's area, the supplementary motor association area and possibly the cerebellum. More uncertainty exists regarding the role of the prefrontal cortex in working memory. Whereas single cell studies in non-human primates and functional imaging studies in humans have suggested an extension of the ventral and dorsal path into different subregions of the prefrontal cortex, lesion studies together with recent single-cell and imaging studies point to a non-mnemonic role of the prefrontal cortex, including attentional control of sensory processing, integration of information from different domains, stimulus selection and monitoring of information held in memory. Our own data argue against a modulatory view of the prefrontal cortex and suggest that processes supporting working memory are distributed along ventral and dorsal lateral prefrontal cortex.     

Topographic segregation and convergence of verbal, object, shape and spatial working memory in humans

This functional magnetic resonance imaging study investigates commonalties and differences in working memory (WM) processes employing different types of stimuli. We specifically sought to characterize topographic convergence and segregation with respect to prefrontal cortex involvement using verbal, spatial, real object and shape memory items in a two-back WM task. Both the dorsolateral and ventrolateral prefrontal cortices are conjointly activated across all stimulus types. No stimulus-specific differences in the activation patterns of the prefrontal cortex could be demonstrated giving support to the view of an amodal prefrontal involvement during WM processes. However, extra-frontal regions specialized on feature processing and involved in the preprocessing of the stimuli were selectively activated by these different subtypes of WM. These selectively activated regions are assigned to parts of the ventral and dorsal stream.     

Neural mechanisms of general fluid intelligence

We used an individual-differences approach to test whether general fluid intelligence (gF) is mediated by brain regions that support attentional (executive) control, including subregions of the prefrontal cortex. Forty-eight participants first completed a standard measure of gF (Raven's Advanced Progressive Matrices). They then performed verbal and nonverbal versions of a challenging working-memory task (three-back) while their brain activity was measured using functional magnetic resonance imaging (fMRI). Trials within the three-back task varied greatly in the demand for attentional control because of differences in trial-to-trial interference. On high-interference trials specifically, participants with higher gF were more accurate and had greater event-related neural activity in several brain regions. Multiple regression analyses indicated that lateral prefrontal and parietal regions may mediate the relation between ability (gF) and performance (accuracy despite interference), providing constraints on the neural mechanisms that support gF.     

A functional magnetic resonance imaging study of the effects of pergolide, a dopamine receptor agonist, on component processes of working memory

Working memory is an important cognitive process dependent on a network of prefrontal and posterior cortical regions. In this study we tested the effects of the mixed D1-D2 dopamine receptor agonist pergolide on component processes of human working memory using functional magnetic resonance imaging (fMRI). An event-related trial design allowed separation of the effects on encoding, maintenance, and retrieval processes. Subjects were tested with spatial and object memoranda to investigate modality-specific effects of dopaminergic stimulation. We also measured baseline working memory capacity as previous studies have shown that effects of dopamine agonists vary with working memory span. Pergolide improved reaction time for high-span subjects and impaired reaction time for low-span subjects. This span-dependent change in behavior was accompanied by span-dependent changes in delay-related activity in the premotor cortex. We also found evidence for modality-specific effects of pergolide only during the response period. Pergolide increased activity for spatial memoranda and decreased activity for object memoranda in task-related regions including the prefrontal and parietal cortices.     

State-related and item-related neural correlates of successful memory encoding

Neuroimaging studies show that the efficacy of long-term memory encoding of a stimulus is indexed by transient neural activity elicited by that stimulus. Here, we show that successful memory encoding is also indexed by neural activity that is tonically maintained throughout a study task. Using functional magnetic resonance imaging (fMRI), transient and sustained neural activity were dissociated with a mixed event-related and blocked design. In a series of short task blocks, human subjects made semantic or phonological decisions about visually presented words. After statistically removing item-related activity, we found that the mean level of activity across a task block was correlated with the number of words subsequently remembered from that block. These correlations were found in inferior medial parietal and left prefrontal cortex for the semantic task, and in superior medial parietal cortex for the phonological task. Our findings suggest that state-related activity in these brain regions is involved in memory encoding.     

Effects of Sleep Deprivation on Dissociated Components of Executive Functioning

Study Objectives:

We studied the effects of sleep deprivation on executive functions using a task battery which included a modified Sternberg task, a probed recall task, and a phonemic verbal fluency task. These tasks were selected because they allow dissociation of some important executive processes from non-executive components of cognition.

Design:

Subjects were randomized to a total sleep deprivation condition or a control condition. Performance on the executive functions task battery was assessed at baseline, after 51 h of total sleep deprivation (or no sleep deprivation in the control group), and following 2 nights of recovery sleep, at fixed time of day (11:00). Performance was also measured repeatedly throughout the experiment on a control task battery, for which the effects of total sleep deprivation had been documented in previously published studies.

Setting:

Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring.

Participants:

Twenty-three healthy adults (age range 22–38 y; 11 women). Twelve subjects were randomized to the sleep deprivation condition; the others were controls.

Results:

Performance on the control task battery was considerably degraded during sleep deprivation. Overall performance on the modified Sternberg task also showed impairment during sleep deprivation, as compared to baseline and recovery and compared to controls. However, two dissociated components of executive functioning on this task—working memory scanning efficiency and resistance to proactive interference—were maintained at levels equivalent to baseline. On the probed recall task, resistance to proactive interference was also preserved. Executive aspects of performance on the phonemic verbal fluency task showed improvement during sleep deprivation, as did overall performance on this task.

Conclusion:

Sleep deprivation affected distinct components of cognitive processing differentially. Dissociated non-executive components of cognition in executive functions tasks were degraded by sleep deprivation, as was control task performance. However, the executive functions of working memory scanning efficiency and resistance to proactive interference were not significantly affected by sleep deprivation, nor were dissociated executive processes of phonemic verbal fluency performance. These results challenge the prevailing view that executive functions are especially vulnerable to sleep loss. Our findings also question the idea that impairment due to sleep deprivation is generic to cognitive processes subserved by attention.

Citation:

Tucker AM; Whitney P; Belenky G; Hinson JM; Van Dongen HPA. Effects of sleep deprivation on dissociated components of executive functioning. SLEEP 2010;33(1):47-57.     

Decreasing task-related brain activity over repeated functional MRI scans and sessions with no change in performance: implications for serial investigations

For prospective functional imaging studies of learning and for clinical studies of recovery or disease progression, it is important that the magnitude of brain activity does not exhibit a trend over repeated sessions in the absence of changes in task performance. This may confuse the interpretation of proposed mechanisms. The objective of this study was to use functional magnetic resonance imaging to determine if a linear trend in brain activity was present for simple and commonly used motor and cognitive tasks. Fourteen healthy individuals participated in three sessions on different days during which four scans each of a finger flexion task and a working memory task were performed in a block design. The general linear model was used to determine brain regions exhibiting activity differences between sessions conducted on different days, as well as between scans performed within the same session. Task-related brain activity decreased over sessions and scans in prefrontal and frontal cortices for both tasks. No increases, nor quadratic trends, were detected. Activity within premotor and ipsilateral primary somatosensory cortex decreased over scans for externally cued finger flexion and over sessions for self-paced finger flexion. Activity within parietal cortex and contralateral supplementary motor area decreased over sessions for all forms of finger flexion. These results suggest that motor planning and sensory regions, as well as frontal and parietal cortices, exhibit linear decreasing brain activity over repeated sessions in the absence of changes in task performance for even the simplest block design paradigms.     

Integration of diverse information in working memory within the frontal lobe

Ability to integrate diverse forms of information in current thought, or working memory, is essential for human reasoning and problem solving. We used functional imaging to identify brain regions preferentially involved in maintaining integrated versus unintegrated information in working memory. For equal amounts of verbal and spatial information, activation of prefrontal cortex was greater for maintaining integrated rather than unintegrated representations. Posterior brain regions showed the opposite pattern. These results demonstrate frontal-lobe specialization in maintaining working-memory representations that integrate verbal and spatial information. The role of prefrontal cortex in integrating multiple forms of information in working memory may underlie its unique contribution to high-level cognition that demands flexible mental representations.     

Reproducibility of changes in behaviour and fMRI activation associated with sleep deprivation in a working memory task

STUDY OBJECTIVES: Although the stability of inter-individual differences in vulnerability to sleep deprivation has been shown behaviourally, the neural basis for these differences has yet to be uncovered. In this study, we assessed the reproducibility of fMRI activation and performance on a working memory task before and after 24 hours of sleep deprivation (SD). DESIGN: All volunteers underwent 2 sessions (pairs of fMRI scans) at rested wakefulness (RW) and after SD. PARTICIPANTS: 19 healthy, right-handed subjects (mean age = 21.37 +/- 1.54 years). MEASUREMENTS AND RESULTS: Brain activation was highly correlated across sessions in a frontoparietal network previously implicated in working memory function. The magnitude of decline in this activation after SD was preserved in bilateral parietal regions. Among several behavioural metrics investigated, the most robust marker of vulnerability to SD was the change in the intra-individual variability of reaction times. This was shown to be both stable over time and correlated with the drop in left parietal activation from RW to SD in both experimental sessions. CONCLUSIONS: Because of its reproducibility, the modulation of parietal activation may provide a good physiological marker of vulnerability to SD.     

Neurophysiological correlates of increased verbal working memory in high-dissociative participants: a functional MRI study

BACKGROUND: Dissociation, defined as a disruption in usually integrated mental functions, is found not only in DSM-IV dissociative disorders, but also in post-traumatic stress disorder and eating disorders. Dissociative phenomena are also common in the general population, and may reflect a constitutionally determined cognitive style rather than a pathological trait acquired through experiencing adverse life events. In pathological dissociation, evidence has been presented for episodic memory dysfunction. In contrast, in high-dissociative subjects increased performance has been found for episodic memory and dual task performance. These findings have been linked to changes in working memory capacity. METHOD: In the present study, the authors sought to extend these findings by using functional magnetic resonance imaging during performance of two parametric working memory tasks. We tested 21 healthy low- and high-dissociative participants. RESULTS: High-dissociative participants performed slightly better during both tasks. Imaging data showed that both groups activated similar networks for both tasks, i.e. (bilateral) dorsolateral (DL) and ventrolateral prefrontal cortex (PFC), parietal cortex, and supplementary motor area. Group x task interactions were found in the high-dissociative group in L DLPFC and L parietal cortex; in the low-dissociative group in R fusiform gyrus. The differences in the high-dissociative group were independent from performance differences, implying that high-dissociative subjects generally recruit this network to a greater extent. CONCLUSIONS: These results confirm earlier findings using a verbal WM task in high-dissociative participants, and are compatible with the conceptualization of non-pathological dissociation as an information-processing style, characterized by distinct attentional and mnemonic abilities.     

Mapping of semantic, phonological, and orthographic verbal working memory in normal adults with functional magnetic resonance imaging.

Twelve neurologically normal participants (4 men and 8 women) performed semantic, phonological, and orthographic working memory tasks and a control task during functional magnetic resonance imaging. Divergent regions of the posterior left hemisphere used for decoding and storage of information emerged in each working memory versus control task comparison. These regions were consistent with previous literature on processing mechanisms for semantic, phonological, and orthographic information. Further, working memory versus control task differences extended into the left frontal lobe, including premotor cortex, and even into subcortical structures. Findings were consistent with R. C. Martin and C. Romani's (1994) contention that different forms of verbal working memory exist and further suggest that a reconceptualization of premotor cortex functions is needed.