Can transcranial direct current stimulation combined with interactive computerized cognitive training boost cognition and gait performance in older adults with mild cognitive impairment? a randomized controlled trial.

BACKGROUND: Older adults with Mild Cognitive Impairment (MCI) are often subject to cognitive and gait deficits. Interactive Computerized Cognitive Training (ICCT) may improve cognitive function; however, the effect of such training on gait performance is limited. Transcranial Direct Current Stimulation (tDCS) improves cognition and gait performance. It remains unclear whether combining tDCS with ICCT produces an enhanced synergistic effect on cognition and complex gait performance relative to ICCT alone. This study aimed to compare the effects of tDCS combined with ICCT on cognition and gait performance in older adults with MCI. METHOD: Twenty-one older adults with MCI were randomly assigned to groups receiving either anodal tDCS and ICCT ( tDCS + ICCT ) or sham tDCS and ICCT ( sham + ICCT ). Participants played Nintendo Switch cognitive games for 40 min per session, simultaneously receiving either anodal or sham tDCS over the left dorsolateral prefrontal cortex for the first 20 min. Cognitive and gait assessments were performed before and after 15 training sessions. RESULTS: The global cognition, executive function, and working-memory scores improved in both groups, but there were no significant interaction effects on cognitive outcomes. Additionally, the group × time interactions indicated that tDCS + ICCT significantly enhanced dual-task gait performance in terms of gait speed (p = 0.045), variability (p = 0.016), and dual-task cost (p = 0.039) compared to sham + ICCT. CONCLUSION: The combined effect of tDCS and ICCT on cognition was not superior to that of ICCT alone; however, it had a significant impact on dual-task gait performance. Administering tDCS as an adjunct to ICCT may thus provide additional benefits for older adults with MCI. TRIAL REGISTRATION: This trial was registered at http://www. CLINICALTRIALS: in.th/ (TCTR 20,220,328,009).

Decision-making impairment under ambiguity but not under risk may underlie medication overuse in patients with chronic migraine.

OBJECTIVE: To explore whether patients with chronic migraine and medication overuse headache (CM + MOH) present with decision-making deficit. BACKGROUND: Factors underlying MOH in patients with CM remain unclear. Whether the process of decision-making plays a role in MOH is still controversial. Decision-making varies in the degree of uncertainty: under ambiguity where the probability of outcome is unknown, and under risk where probabilities are known. METHODS: Decisions under ambiguity and risk were assessed with the Iowa Gambling Task and the Cambridge Gambling Task, respectively, whereas executive function was assessed by the Wisconsin Card Sorting Test. RESULTS: A total of 75 participants: 25 patients with CM + MOH, 25 with CM, and 25 age- and sex-similar healthy controls (HCs), completed this cross-sectional study. There was no significant difference in headache profiles except for more frequent analgesic use (mean ± SD: 23.5 ± 7.6 vs. 6.8 ± 3.4 days; p < 0.001) and higher Severity of Dependence Scores (median [25th-75th percentile]: 8 [5-11] vs. 1 [0-4]; p < 0.001) in patients with CM + MOH compared to CM. Total net score (mean ± SD) on the Iowa Gambling Task in patients with CM + MOH, CM, and HCs were - 8.1 ± 28.7, 10.9 ± 29.6, and 14.2 ± 28.8, respectively. There was a significant difference between the three groups (F(2, 72) = 4.28, p = 0.017), with patients with CM + MOH making significantly more disadvantageous decisions than patients with CM (p = 0.024) and HCs (p = 0.008), while the CM and HC groups did not differ (p = 0.690). By contrast, there was no significant difference between the groups in the Cambridge Gambling Task and the Wisconsin Card Sorting Test. Furthermore, performance on the Iowa Gambling Task was inversely correlated with analgesic consumption (r = -0.41, p = 0.003), suggesting that decision-making under ambiguity may be related to MOH. CONCLUSIONS: Our data suggest that patients with CM + MOH had impaired decisions under ambiguous, but not risky situations. This dissociation indicates disrupted emotional feedback processing rather than executive dysfunction, which may underlie the pathogenesis of MOH.

Transcranial Magnetic Stimulation and the Understanding of Behavior.

The development of the use of transcranial magnetic stimulation (TMS) in the study of psychological functions has entered a new phase of sophistication. This is largely due to an increasing physiological knowledge of its effects and to its being used in combination with other experimental techniques. This review presents the current state of our understanding of the mechanisms of TMS in the context of designing and interpreting psychological experiments. We discuss the major conceptual advances in behavioral studies using TMS. There are meaningful physiological and technical achievements to review, as well as a wealth of new perceptual and cognitive experiments. In doing so we summarize the different uses and challenges of TMS in mental chronometry, perception, awareness, learning, and memory.

High-Frequency External Muscle Stimulation Reduces Depressive Symptoms in Older Male Veterans: A Pilot Study.

OBJECTIVE: Late-life depression (LLD) is a severe public health problem. Given that pharmacological treatments for LLD are limited by their side effects, development of efficient and tolerable nonpharmacological treatment for LLD is urgently required. This study investigated whether high-frequency external muscle stimulation could reduce depressive symptoms in LLD. METHODS: Twenty-two older male veterans with major depression were recruited and randomized into a treatment (n = 9) or sham control group (n = 13). The groups received high-frequency external muscle stimulation or sham intervention 3 times per week for 12 weeks. Clinical symptoms and muscle strength were evaluated at baseline and every 2 weeks. RESULTS: The 2 groups were homogeneous in age, baseline clinical symptoms, and muscle strength. The treatment group showed significant improvement in depression and anxiety scores and muscle strength (all P < .01), whereas the control group showed no significant change after the 12-week follow-up. Compared to the control group, the treatment group showed significant improvements in depression (Geriatric Depression Scale, P = .009; Hamilton Depression Rating Scale, P = .007) and anxiety scores (HAMA, P = .008) and muscle strength (all P < .001). Changes in depression and anxiety levels were significantly correlated with changes in muscle strength after the study. In the treatment group, we observed a trend of correlation between the reduction in depression and muscle strength gains. CONCLUSION: High-frequency external muscle stimulation appears to be an effective treatment for older patients with LLD. Large studies with more tests and/or conducted in different populations are warranted to validate these preliminary findings.

Alpha Oscillations Are Causally Linked to Inhibitory Abilities in Ageing.

Aging adults typically show reduced ability to ignore task-irrelevant information, an essential skill for optimal performance in many cognitive operations, including those requiring working memory (WM) resources. In a first experiment, young and elderly human participants of both genders performed an established WM paradigm probing inhibitory abilities by means of valid, invalid, and neutral retro-cues. Elderly participants showed an overall cost, especially in performing invalid trials, whereas younger participants' general performance was comparatively higher, as expected.Inhibitory abilities have been linked to alpha brain oscillations but it is yet unknown whether in aging these oscillations (also typically impoverished) and inhibitory abilities are causally linked. To probe this possible causal link in aging, we compared in a second experiment parietal alpha-transcranial alternating current stimulation (tACS) with either no stimulation (Sham) or with two control stimulation frequencies (theta- and gamma-tACS) in the elderly group while performing the same WM paradigm. Alpha- (but not theta- or gamma-) tACS selectively and significantly improved performance (now comparable to younger adults' performance in the first experiment), particularly for invalid cues where initially elderly showed the highest costs. Alpha oscillations are therefore causally linked to inhibitory abilities and frequency-tuned alpha-tACS interventions can selectively change these abilities in the elderly.SIGNIFICANCE STATEMENT Ignoring task-irrelevant information, an ability associated to rhythmic brain activity in the alpha frequency band, is fundamental for optimal performance. Indeed, impoverished inhibitory abilities contribute to age-related decline in cognitive functions like working memory (WM), the capacity to briefly hold information in mind. Whether in aging adults alpha oscillations and inhibitory abilities are causally linked is yet unknown. We experimentally manipulated frequency-tuned brain activity using transcranial alternating current stimulation (tACS), combined with a retro-cue paradigm assessing WM and inhibition. We found that alpha-tACS induced a significant improvement in target responses and misbinding errors, two indexes of inhibition. We concluded that in aging alpha oscillations are causally linked to inhibitory abilities, and that despite being impoverished, these abilities are still malleable.

Correction: Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex.

[This corrects the article DOI: 10.1371/journal.pbio.1002262.].

Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex.

Although psychological and computational models of time estimation have postulated the existence of neural representations tuned for specific durations, empirical evidence of this notion has been lacking. Here, using a functional magnetic resonance imaging (fMRI) adaptation paradigm, we show that the inferior parietal lobule (IPL) (corresponding to the supramarginal gyrus) exhibited reduction in neural activity due to adaptation when a visual stimulus of the same duration was repeatedly presented. Adaptation was strongest when stimuli of identical durations were repeated, and it gradually decreased as the difference between the reference and test durations increased. This tuning property generalized across a broad range of durations, indicating the presence of general time-representation mechanisms in the IPL. Furthermore, adaptation was observed irrespective of the subject's attention to time. Repetition of a nontemporal aspect of the stimulus (i.e., shape) did not produce neural adaptation in the IPL. These results provide neural evidence for duration-tuned representations in the human brain.

Learning to integrate versus inhibiting information is modulated by age.

Cognitive training aiming at improving learning is often successful, but what exactly underlies the observed improvements and how these differ across the age spectrum are currently unknown. Here we asked whether learning in young and older people may reflect enhanced ability to integrate information required to perform a cognitive task or whether it may instead reflect the ability to inhibit task-irrelevant information for successful task performance. We trained 30 young and 30 aging human participants on a numerosity discrimination task known to engage the parietal cortex and in which cue-integration and inhibitory abilities can be distinguished. We coupled training with parietal, motor, or sham transcranial random noise stimulation, known for modulating neural activity. Numerosity discrimination improved after training and was maintained long term, especially in the training + parietal stimulation group, regardless of age. Despite the quantitatively similar improvement in the two age groups, the content of learning differed remarkably: aging participants improved more in inhibitory abilities, whereas younger subjects improved in cue-integration abilities. Moreover, differences in the content of learning were reflected in different transfer effects to untrained but related abilities: in the younger group, improvements in cue integration paralleled improvements in continuous quantity (time and space), whereas in the elderly group, improvements in numerosity-based inhibitory abilities generalized to other measures of inhibition and corresponded to a decline in space discrimination, possibly because conflicting learning resources are used in numerosity and continuous quantity processing. These results indicate that training can enhance different, age-dependent cognitive processes and highlight the importance of identifying the exact processes underlying learning for effective training programs.

Transcranial Direct Current Stimulation of the Motor Cortex Biases Action Choice in a Perceptual Decision Task.

One of the multiple interacting systems involved in the selection and execution of voluntary actions is the primary motor cortex (PMC). We aimed to investigate whether the transcranial direct current stimulation (tDCS) of this area can modulate hand choice. A perceptual decision-making task was administered. Participants were asked to classify rectangles with different height-to-width ratios into horizontal and vertical rectangles using their right and left index fingers while their PMC was stimulated either bilaterally or unilaterally. Two experiments were conducted with different stimulation conditions: the first experiment (n = 12) had only one stimulation condition (bilateral stimulation), and the second experiment (n = 45) had three stimulation conditions (bilateral, anodal unilateral, and cathodal unilateral stimulations). The second experiment was designed to confirm the results of the first experiment and to further investigate the effects of anodal and cathodal stimulations alone in the observed effects. Each participant took part in two sessions. The laterality of stimulation was reversed over the two sessions. Our results showed that anodal stimulation of the PMC biases participants' responses toward using the contralateral hand whereas cathodal stimulation biases responses toward the ipsilateral hand. Brain stimulation also modulated the RT of the left hand in all stimulation conditions: Responses were faster when the response bias was in favor of the left hand and slower when the response bias was against it. We propose two possible explanations for these findings: the perceptual bias account (bottom-up effects of stimulation on perception) and the motor-choice bias account (top-down modulation of the decision-making system by facilitation of response in one hand over the other). We conclude that motor responses and the choice of hand can be modulated using tDCS.

Interaction of numerosity and time in prefrontal and parietal cortex.

It has been proposed that numerical and temporal information are processed by partially overlapping magnitude systems. Interactions across different magnitude domains could occur both at the level of perception and decision-making. However, their neural correlates have been elusive. Here, using functional magnetic resonance imaging in humans, we show that the right intraparietal cortex (IPC) and inferior frontal gyrus (IFG) are jointly activated by duration and numerosity discrimination tasks, with a congruency effect in the right IFG. To determine whether the IPC and the IFG are involved in response conflict (or facilitation) or modulation of subjective passage of time by numerical information, we examined their functional roles using transcranial magnetic stimulation (TMS) and two different numerosity-time interaction tasks: duration discrimination and time reproduction tasks. Our results show that TMS of the right IFG impairs categorical duration discrimination, whereas that of the right IPC modulates the degree of influence of numerosity on time perception and impairs precise time estimation. These results indicate that the right IFG is specifically involved at the categorical decision stage, whereas bleeding of numerosity information on perception of time occurs within the IPC. Together, our findings suggest a two-stage model of numerosity-time interactions whereby the interaction at the perceptual level occurs within the parietal region and the interaction at categorical decisions takes place in the prefrontal cortex.

Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe.

Improvement in performance following cognitive training is known to be further enhanced when coupled with brain stimulation. Here we ask whether training-induced changes can be maintained long term and, crucially, whether they can extend to other related but untrained skills. We trained overall 40 human participants on a simple and well established paradigm assessing the ability to discriminate numerosity--or the number of items in a set--which is thought to rely on an "approximate number sense" (ANS) associated with parietal lobes. We coupled training with parietal stimulation in the form of transcranial random noise stimulation (tRNS), a noninvasive technique that modulates neural activity. This yielded significantly better and longer lasting improvement (up to 16 weeks post-training) of the precision of the ANS compared with cognitive training in absence of stimulation, stimulation in absence of cognitive training, and cognitive training coupled to stimulation to a control site (motor areas). Critically, only ANS improvement induced by parietal tRNS + Training transferred to proficiency in other parietal lobe-based quantity judgment, i.e., time and space discrimination, but not to quantity-unrelated tasks measuring attention, executive functions, and visual pattern recognition. These results indicate that coupling intensive cognitive training with tRNS to critical brain regions resulted not only in the greatest and longer lasting improvement of numerosity discrimination, but importantly in this enhancement being transferable when trained and untrained abilities are carefully chosen to share common cognitive and neuronal components.

Dissociable neuroanatomical correlates of subsecond and suprasecond time perception.

The ability to estimate durations varies across individuals. Although previous studies have reported that individual differences in perceptual skills and cognitive capacities are reflected in brain structures, it remains unknown whether timing abilities are also reflected in the brain anatomy. Here, we show that individual differences in the ability to estimate subsecond and suprasecond durations correlate with gray matter (GM) volume in different parts of cortical and subcortical areas. Better ability to discriminate subsecond durations was associated with a larger GM volume in the bilateral anterior cerebellum, whereas better performance in estimating the suprasecond range was associated with a smaller GM volume in the inferior parietal lobule. These results indicate that regional GM volume is predictive of an individual's timing abilities. These morphological results support the notion that subsecond durations are processed in the motor system, whereas suprasecond durations are processed in the parietal cortex by utilizing the capacity of attention and working memory to keep track of time.

The angular gyrus and visuospatial attention in decision-making under risk.

Recent neuroimaging studies on decision-making under risk indicate that the angular gyrus (AG) is sensitive to the probability and variance of outcomes during choice. A separate body of research has established the AG as a key area in visual attention. The current study used repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers to test whether the causal contribution of the AG to decision-making is independent of or linked to the guidance of visuospatial attention. A within-subject design compared decision making on a laboratory gambling task under three conditions: following rTMS to the AG, following rTMS to the premotor cortex (PMC, as an active control condition) and without TMS. The task presented two different trial types, 'visual' and 'auditory' trials, which entailed a high versus minimal demand for visuospatial attention, respectively. Our results showed a systematic effect of rTMS to the AG upon decision-making behavior in visual trials. Without TMS and following rTMS to the control region, decision latencies reflected the odds of winning; this relationship was disrupted by rTMS to the AG. In contrast, no significant effects of rTMS to the AG (or to the PMC) upon choice behavior in auditory trials were found. Thus, rTMS to the AG affected decision-making only in the task condition requiring visuospatial attention. The current findings suggest that the AG contributes to decision-making by guiding attention to relevant information about reward and punishment in the visual environment.

Left insular cortex and left SFG underlie prismatic adaptation effects on time perception: evidence from fMRI.

Prismatic adaptation (PA) has been shown to affect left-to-right spatial representations of temporal durations. A leftward aftereffect usually distorts time representation toward an underestimation, while rightward aftereffect usually results in an overestimation of temporal durations. Here, we used functional magnetic resonance imaging (fMRI) to study the neural mechanisms that underlie PA effects on time perception. Additionally, we investigated whether the effect of PA on time is transient or stable and, in the case of stability, which cortical areas are responsible of its maintenance. Functional brain images were acquired while participants (n=17) performed a time reproduction task and a control-task before, immediately after and 30 min after PA inducing a leftward aftereffect, administered outside the scanner. The leftward aftereffect induced an underestimation of time intervals that lasted for at least 30 min. The left anterior insula and the left superior frontal gyrus showed increased functional activation immediately after versus before PA in the time versus the control-task, suggesting these brain areas to be involved in the executive spatial manipulation of the representation of time. The left middle frontal gyrus showed an increase of activation after 30 min with respect to before PA. This suggests that this brain region may play a key role in the maintenance of the PA effect over time.

Transcranial electrical brain stimulation modulates neuronal tuning curves in perception of numerosity and duration.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method with many putative applications and reported to effectively modulate behaviour. However, its effects have yet to be considered at a computational level. To address this we modelled the tuning curves underlying the behavioural effects of stimulation in a perceptual task. Participants judged which of the two serially presented images contained more items (numerosity judgement task) or was presented longer (duration judgement task). During presentation of the second image their posterior parietal cortices (PPCs) were stimulated bilaterally with opposite polarities for 1.6s. We also examined the impact of three stimulation conditions on behaviour: anodal right-PPC and cathodal left-PPC (rA-lC), reverse order (lA-rC) and no-stimulation condition. Behavioural results showed that participants were more accurate in numerosity and duration judgement tasks when they were stimulated with lA-rC and rA-lC stimulation conditions respectively. Simultaneously, a decrease in performance on numerosity and duration judgement tasks was observed when the stimulation condition favoured the other task. Thus, our results revealed a double-dissociation of laterality and task. Importantly, we were able to model the effects of stimulation on behaviour. Our computational modelling showed that participants' superior performance was attributable to a narrower tuning curve--smaller standard deviation of detection noise. We believe that this approach may prove useful in understanding the impact of brain stimulation on other cognitive domains.

Vestibular activation differentially modulates human early visual cortex and V5/MT excitability and response entropy.

Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC.

Two critical and functionally distinct stages of face and body perception.

Cortical regions that respond preferentially to particular object categories, such as faces and bodies, are essential for visual perception of these object categories. However, precisely when these regions play a causal role in recognition of their preferred categories is unclear. Here we addressed this question using transcranial magnetic stimulation (TMS). Across a series of experiments, TMS was delivered over the functionally localized right occipital face area (rOFA) or right extrastriate body area (rEBA) at different latencies, up to 150 ms, after stimulus onset while adult human participants performed delayed match-to-sample tasks on face and body stimuli. Results showed that TMS disrupted task performance during two temporally distinct time periods after stimulus onset, the first at 40/50 ms and the second at 100/110 ms. These two time periods exhibited functionally distinct patterns of impairment: TMS delivered during the early time period (at 40/50 ms) disrupted task performance for both preferred (faces at rOFA and bodies at rEBA) and nonpreferred (bodies at rOFA and faces at rEBA) categories. In contrast, TMS delivered during the later time period (at 100/110 ms) disrupted task performance for the preferred category only of each area (faces at rOFA and bodies at rEBA). These results indicate that category-selective cortical regions are critical for two functionally distinct stages of visual object recognition: an early, presumably preparatory stage that is not category selective occurring almost immediately after stimulus onset, followed by a later stage of category-specific perceptual processing.

Unleashing potential: transcranial direct current stimulation over the right posterior parietal cortex improves change detection in low-performing individuals.

The limits of human visual short-term memory (VSTM) have been well documented, and recent neuroscientific studies suggest that VSTM performance is associated with activity in the posterior parietal cortex. Here we show that artificially elevating parietal activity via positively charged electric current through the skull can rapidly and effortlessly improve people's VSTM performance. This artificial improvement, however, comes with an interesting twist: it interacts with people's natural VSTM capability such that low performers who tend to remember less information benefitted from the stimulation, whereas high performers did not. This behavioral dichotomy is explained by event-related potentials around the parietal regions: low performers showed increased waveforms in N2pc and contralateral delay activity (CDA), which implies improvement in attention deployment and memory access in the current paradigm, respectively. Interestingly, these components are found during the presentation of the test array instead of the retention interval, from the parietal sites ipsilateral to the target location, thus suggesting that transcranial direct current stimulation (tDCS) was mainly improving one's ability to suppress no-change distractors located on the irrelevant side of the display during the comparison stage. The high performers, however, did not benefit from tDCS as they showed equally large waveforms in N2pc and CDA, or SPCN (sustained parietal contralateral negativity), before and after the stimulation such that electrical stimulation could not help any further, which also accurately accounts for our behavioral observations. Together, these results suggest that there is indeed a fixed upper limit in VSTM, but the low performers can benefit from neurostimulation to reach that maximum via enhanced comparison processes, and such behavioral improvement can be directly quantified and visualized by the magnitude of its associated electrophysiological waveforms.

Rapid changes in brain structure predict improvements induced by perceptual learning.

Practice-dependent changes in brain structure can occur in task relevant brain regions as a result of extensive training in complex motor tasks and long-term cognitive training but little is known about the impact of visual perceptual learning on brain structure. Here we studied the effect of five days of visual perceptual learning in a motion-color conjunction search task using anatomical MRI. We found rapid changes in gray matter volume in the right posterior superior temporal sulcus, an area sensitive to coherently moving stimuli, that predicted the degree to which an individual's performance improved with training. Furthermore, behavioral improvements were also predicted by volumetric changes in an extended white matter region underlying the visual cortex. These findings point towards quick and efficient plastic neural mechanisms that enable the visual brain to deal effectively with changing environmental demands.

Sleep facilitates long-term face adaptation.

Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.