Decreased cortical response to verbal working memory following sleep deprivation

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.     

Sleep stabilizes visuomotor adaptation memory: a functional magnetic resonance imaging study

The beneficial effect of sleep on motor memory consolidation is well known for motor sequence memory, but remains unsettled for visuomotor adaptation in humans. The aim of this study was to characterize more clearly the influence of sleep on consolidation of visuomotor adaptation using a between‐subjects functional magnetic resonance imaging (fMRI) design contrasting sleep to total sleep deprivation. Our behavioural results, based on seven different parameters, show that sleep stabilizes performance whereas sleep deprivation deteriorates it. During training, while a set of cerebellar, striatal and cortical areas is activated in proportion to performance improvement, the recruitment of the hippocampus and frontal cortex protects motor memory against the detrimental effects of sleep deprivation. During retest after sleep loss a cerebello–cortical network, usually involved in the earliest stage of learning, was recruited to perform the task. In contrast, no changes in cerebral activity were observed after sleep, suggesting that it may only support the stabilization of the visuomotor adaptation memory trace.     

Striatal activation during acquisition of a cognitive skill.

The striatum is thought to play an essential role in the acquisition of a wide range of motor, perceptual, and cognitive skills, but neuroimaging has not yet demonstrated striatal activation during nonmotor skill learning. Functional magnetic resonance imaging was performed while participants learned probabilistic classification, a cognitive task known to rely on procedural memory early in learning and declarative memory later in learning. Multiple brain regions were active during probabilistic classification compared with a perceptual-motor control task, including bilateral frontal cortices, occipital cortex, and the right caudate nucleus in the striatum. The left hippocampus was less active bilaterally during probabilistic classification than during the control task, and the time course of this hippocampal deactivation paralleled the expected involvement of medial temporal structures based on behavioral studies of amnesic patients. Findings provide initial evidence for the role of frontostriatal systems in normal cognitive skill learning.     

Hippocampal and medial prefrontal cortical volume is associated with overnight declarative memory consolidation independent of specific sleep oscillations

The current study was designed to further clarify the influence of brain morphology, sleep oscillatory activity and age on memory consolidation. Specifically, we hypothesized, that a smaller volume of hippocampus, parahippocampal and medial prefrontal cortex negatively impacts declarative, but not procedural, memory consolidation. Explorative analyses were conducted to demonstrate whether a decrease in slow‐wave activity negatively impacts declarative memory consolidation, and whether these factors mediate age effects on memory consolidation. Thirty‐eight healthy participants underwent an acquisition session in the evening and a retrieval session in the morning after night‐time sleep with polysomnographic monitoring. Declarative memory was assessed with the paired‐associate word list task, while procedural memory was tested using the mirror‐tracing task. All participants underwent high‐resolution magnetic resonance imaging. Participants with smaller hippocampal, parahippocampal and medial prefrontal cortex volumes displayed a reduced overnight declarative, but not procedural memory consolidation. Mediation analyses showed significant age effects on overnight declarative memory consolidation, but no significant mediation effects of brain morphology on this association. Further mediation analyses showed that the effects of age and brain morphology on overnight declarative memory consolidation were not mediated by polysomnographic variables or sleep electroencephalogram spectral power variables. Thus, the results suggest that the association between age, specific brain area volume and overnight memory consolidation is highly relevant, but does not necessarily depend on slow‐wave sleep as previously conceptualized.     

The impact of sleep on complex gross‐motor adaptation in adolescents

Sleep has been shown to facilitate the consolidation of newly acquired motor memories in adults. However, the role of sleep in motor memory consolidation is less clear in children and adolescents, especially concerning real‐life gross‐motor skills. Therefore, we investigated the effects of sleep and wakefulness on a complex gross‐motor adaptation task by using a bicycle with an inverse steering device. A total of 29 healthy adolescents aged between 11 and 14 years (five female) were either trained to ride an inverse steering bicycle (learning condition) or a stationary bicycle (control condition). Training took place in the morning (wake, n = 14) or in the evening (sleep, n = 15) followed by a 9‐hr retention interval and a subsequent re‐test session. Slalom cycling performance was assessed by speed (riding time) and accuracy (standard deviation of steering angle) measures. Behavioural results showed no evidence for sleep‐dependent memory consolidation. However, overnight gains in accuracy were associated with an increase in left hemispheric N2 slow sleep spindle activity from control to learning night. Furthermore, decreases in REM and tonic REM duration were related to higher overnight improvements in accuracy. Regarding speed, an increase in REM and tonic REM duration was favourable for higher overnight gains in riding time. Thus, although not yet detectable on a behavioural level, sleep seemed to play a role in the acquisition of gross‐motor skills. A promising direction for future research is to focus on the possibility of delayed performance gains in adolescent populations.     

The effect of musical training on the neural correlates of math processing: a functional magnetic resonance imaging study in humans

The neural correlates of the previously hypothesized link between formal musical training and mathematics performance are investigated using functional magnetic resonance imaging (fMRI). FMRI was performed on fifteen normal adults, seven with musical training since early childhood, and eight without, while they mentally added and subtracted fractions. Musical training was associated with increased activation in the left fusiform gyrus and prefrontal cortex, and decreased activation in visual association areas and the left inferior parietal lobule during the mathematical task. We hypothesize that the correlation between musical training and math proficiency may be associated with improved working memory performance and an increased abstract representation of numerical quantities.     

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.     

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.     

Functional segregation of the inferior frontal gyrus for syntactic processes: a functional magnetic-resonance imaging study

We used functional magnetic resonance imaging in 18 normal volunteers to determine whether there is separate representation of syntactic, semantic, and verbal working memory processing in the left inferior frontal gyrus (GFi). We compared a sentence comprehension task with a short-term memory maintenance task to identify syntactic and semantic processing regions. To investigate the effects of syntactic and verbal working memory load while minimizing the differences in semantic processes, we used comprehension tasks with garden-path (GP) sentences, which require re-parsing, and non-garden-path (NGP) sentences. Compared with the short-term memory task, sentence comprehension activated the left GFi, including Brodmann areas (BAs) 44, 45, and 47, and the left superior temporal gyrus. In GP versus NGP sentences, there was greater activity in the left BAs 44, 45, and 46 extending to the left anterior insula, the pre-supplementary motor area, and the right cerebellum. In the left GFi, verbal working memory activity was located more dorsally (BA 44/45), semantic processing was located more ventrally (BA 47), and syntactic processing was located in between (BA 45). These findings indicate a close relationship between semantic and syntactic processes, and suggest that BA 45 might link verbal working memory and semantic processing via syntactic unification processes.     

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.     

Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep

One function of sleep is hypothesized to be the reprocessing and consolidation of memory traces (Smith, 1995; Gais et al., 2000; McGaugh, 2000; Stickgold et al., 2000). At the cellular level, neuronal reactivations during post-training sleep in animals have been observed in hippocampal (Wilson and McNaughton, 1994) and cortical (Amzica et al., 1997) neuronal populations. At the systems level, using positron emission tomography, we have recently shown that some brain areas reactivated during rapid-eye-movement sleep in human subjects previously trained on an implicit learning task (a serial reaction time task) (Maquet et al., 2000). These cortical reactivations, located in the left premotor area and bilateral cuneus, were thought to reflect the reprocessing--possibly the consolidation--of memory traces during post-training rapid-eye-movement sleep. Here, the experience-dependent functional connectivity of these brain regions is examined. It is shown that the left premotor cortex is functionally more correlated with the left posterior parietal cortex and bilateral pre-supplementary motor area during rapid-eye-movement sleep of subjects previously trained to the reaction time task compared to rapid-eye-movement sleep of untrained subjects. The increase in functional connectivity during post-training rapid-eye-movement sleep suggests that the brain areas reactivated during post-training rapid-eye-movement sleep participate in the optimization of the network that subtends subject's visuo-motor response. The optimization of this visuo-motor network during sleep could explain the gain in performance observed during the following day.     

Suppression of the non-dominant motor cortex during bimanual symmetric finger movement: a functional magnetic resonance imaging study

Patterns of bimanual coordination in which homologous muscles are simultaneously active are more stable than those in which homologous muscles are engaged in an alternating fashion. This may be attributable to the stronger involvement of the dominant motor cortex in ipsilateral hand movements via interaction with the non-dominant motor system, known as neural crosstalk. We used functional magnetic resonance imaging to investigate the neural representation of the interhemispheric interaction during bimanual mirror movements. Thirteen right-handed subjects completed four conditions: sequential finger tapping using the right and left index and middle fingers, bimanual mirror and parallel finger tapping. Auditory cues (3 Hz) were used to keep the tapping frequency constant. Task-related activation in the right primary motor cortex was significantly less prominent during mirror than unimanual left-handed movements. This was mirror- and non-dominant side-specific; parallel movements did not cause such a reduction, and the left primary motor cortex showed no such differential activation across the unimanual right, bimanual mirror, and bimanual parallel conditions. Reducing the contralateral innervation of the left hand may increase the fraction of the force command to the left hand coming from the left primary motor cortex, enhancing the neural crosstalk.     

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.     

Context modulates processing of speech sounds in the right auditory cortex of human subjects

Functionally, the cerebellum is not only involved in motor control but is also thought to influence higher cognitive function including language. Anatomical data would suggest crossed reciprocal connections between the cerebellum and higher order cortical association areas. In the following study, one left- and one right-handed female volunteer underwent functional magnetic resonance imaging in a conventional block design. Regions of activation were detected after performance of a silent verbal fluency task inside the scanner. In the right-handed volunteer we found an activation of the left fronto-parietal cortex and the right cerebellar hemisphere, while in the left-handed volunteer the activation was seen in the right fronto-parieto-temporal cortex and the left cerebellar hemisphere. These initial results demonstrate that cerebellar activation is contralateral to the activation of the frontal cortex even under conditions of different language dominance. They provide evidence for the hypothesis of a lateralized organization of the cerebellum crossed to the cerebral hemispheres in supporting higher cognitive function.     

健康人大脑和小脑空间记忆认知功能的fMRI研究

本研究应用功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,检测了健康人大脑和小脑参与空间记忆的认知过程。通过对10名右利手健康志愿者进行一项短时空间记忆任务作业的同时进行脑功能磁共振扫描,实验采用组块设计,任务与对照任务交替进行,数据采用SPM99软件进行数据分析和脑功能区定位。结果显示:当统计阈值设定为P<0.0001时,大脑皮层和右侧小脑一起被显著激活;大脑皮层所激活的脑区有双侧顶叶的楔前叶、顶上小叶、缘上回(BA7/40,BA:Brodma-nn Area),双侧前额上、中、下回(BA6/9/47),双侧枕叶和枕颞交界处(BA18/19/37),右侧海马回;左侧中脑黑质及被盖部也被激活。上述结果提示:小脑和大脑皮层一起参与了空间记忆的认知过程。     

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.     

Retrograde effects of triazolam and zolpidem on sleep-dependent motor learning in humans

Drugs that act as allosteric activators at the benzodiazepine site of the gamma-aminobutyric acid (GABA_A) receptor complex are used commonly to treat insomnia but relatively little is known of how such use affects learning and memory. Although anterograde effects on memory acquisition have been shown, possible retrograde effects on consolidation are more relevant when such agents are administered at bedtime. We tested the effects of two GABA_A allosteric activators on sleep-dependent motor skill memory consolidation in 12 healthy male subjects. Subjects slept in a sleep laboratory for four consecutive nights (one accommodation night followed by three experimental nights). Placebo, triazolam 0.375 mg, and zolpidem 10 mg were given to each subject in counterbalanced order on the experimental nights. Polysomnographic (PSG) sleep measurement and sleep-dependent motor learning were assessed at each condition. Triazolam was associated with longer total sleep time and increased Stage 2 sleep. Both zolpidem and triazolam were associated with increased latency to rapid eye movement (REM) sleep. Overnight motor learning correlated with total sleep time in the placebo condition but not in the triazolam or zolpidem conditions. A statistically significant impairment in motor performance occurred overnight in the triazolam condition only. Triazolam, given in sufficient doses to prolong sleep in healthy people, affected overnight motor learning adversely. Zolpidem, in a dose sufficient to prolong REM onset latency but without other effects on PSG-measured sleep, degraded the relationship between total sleep time and overnight motor learning. These data indicate that non-selective or α1-preferring benzodiazepine site allosteric activators can interfere with sleep-dependent memory consolidation.     

Sleep modulates word-pair learning but not motor sequence learning in healthy older adults

Sleep benefits memory across a range of tasks for young adults. However, remarkably little is known of the role of sleep on memory for healthy older adults. We used 2 tasks, 1 assaying motor skill learning and the other assaying nonmotor/declarative learning, to examine off-line changes in performance in young (20-34 years), middle-aged (35-50 years), and older (51-70 years) adults without disordered sleep. During an initial session, conducted either in the morning or evening, participants learned a motor sequence and a list of word pairs. Memory tests were given twice, 12 and 24 hours after training, allowing us to analyze off-line consolidation after a break that included sleep or normal wake. Sleep-dependent performance changes were reduced in older adults on the motor sequence learning task. In contrast, sleep-dependent performance changes were similar for all 3 age groups on the word pair learning task. Age-related changes in sleep or networks activated during encoding or during sleep may contribute to age-related declines in motor sequence consolidation. Interestingly, these changes do not affect declarative memory.     

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.