Is sleep affected after microgravity and hypergravity exposure? A pilot study.

Sleep is known to be affected in space travel and in residents of the international space station. But little is known about the direct effects of gravity changes on sleep, if other factors, such as sleep conditions, are kept constant. Here, as a first exploration, we investigated sleep before and after exposure to short bouts of microgravity and hypergravity during parabolic flights. Sleep was measured through actigraphy and self-report questionnaires in 20 healthy men and women before and after parabolic flight. Higher sleep fragmentation and more awakenings were found in the night after the flight as compared with the night before, which was discrepant from participants' reports showing better and longer sleep after the parabolic flight. Variable levels of experience with parabolic flights did not affect the results, nor did levels of scopolamine, a medication typically taken against motion sickness. Pre-existing sleep problems were related to sleep fragmentation and wake after sleep onset by a quadratic function such that participants with more sleep problems showed lower levels of sleep fragmentation and nighttime awakenings than those with few sleep problems. These novel findings, though preliminary, have important implications for future research, directed at prevention and treatment of sleep problems and their daytime consequences in situations of altered gravity, and possibly in the context of other daytime vestibular challenges as well.

How to deal with sleep problems during heatwaves: practical recommendations from the European Insomnia Network.

Heatwaves are occurring more frequently and are known to affect particularly night-time temperatures. We review here literature on how night-time ambient temperature changes affect body temperature and sleep quality. We then discuss how these temperature effects impact particularly vulnerable populations such as older adults, children, pregnant women, and those with psychiatric conditions. Several ways of dealing with sleep problems in the context of heatwaves are then suggested, adapted from elements of cognitive behavioural therapy for insomnia, with more specific advice for vulnerable populations. By better dealing with sleep problems during heatwaves, general health effects of heatwaves may be more limited. However, given the sparse literature, many links addressed in this review on sleep problems affected by temperature changes should be the focus of future research.

The Executive Functioning Paradox in Substance Use Disorders.

Deficits in neurocognitive functioning are trait-like vulnerabilities that have been widely studied in persons with substance use disorders (SUD), but their role in the craving-use association and relapse vulnerability remains poorly understood. The main objectives of this study were to examine whether executive capacities moderate the magnitude of the craving-substance use relationship, and if this influence is correlated with the functional connectivity of cerebral networks, combining rsfMRI examinations and ecological momentary assessment (EMA). Eighty-six patients beginning outpatient treatment for alcohol, tobacco or cannabis addiction and 40 healthy controls completed neuropsychological tests followed by EMA to collect real-time data on craving. Fifty-four patients and 30 healthy controls also completed a resting-state fMRI before the EMA. Among the patients with SUD, better verbal fluency and resistance to interference capacities were associated with a greater propensity to use substances when the individual was experiencing craving. Preliminary rsfMRI results identified specific networks that interacted with executive performance capacities to influence the magnitude of the craving-use association. Individuals with better executive functioning may be more prone to relapse after craving episodes. Specifically, better resistance to interference and cognitive flexibility skills may reduce attention to distracting stimuli, leading to a greater awareness of craving and susceptibility to use substances.

Mental fatigue correlates with depression of task-related network and augmented DMN activity but spares the reward circuit.

Long-lasting and demanding cognitive activity typically leads to mental fatigue (MF). Indirect evidence suggests that MF may be caused by altered motivational processes. Here, we hypothesized that if MF consists in an alteration of motivational states, brain functional changes induced by MF could specifically affect the brain motivation circuit. In order to test this hypothesis, we devised a functional neuroimaging protocol to detect altered brain activity in reward-related brain regions in relation to cognitively induced mental fatigue. Twenty-five healthy participants underwent a FATIGUE and a CONTROL session on different days. In the FATIGUE session, MF was induced by performing a demanding cognitive task (adapted Stroop task) during 90 min, whereas in the CONTROL session, participants were asked to read magazines for the same period of time. We measured the neural consequences of the MF induction during a working memory task (Missing Number task) while modulating extrinsic motivation with block-wise variations in monetary reward. We also tracked participants' momentary fatigue, anxiety state and intrinsic motivation prior to and following the MF inducement and measurement. Accuracy on the Missing Number Task was lower in the FATIGUE than in the CONTROL condition. Furthermore, subjective MF, but not its behavioral manifestations, was associated with hypoactivity of the task-evoked neural responses. Importantly, activity in regions modulated by reward showed no differences between FATIGUE and CONTROL sessions. In parallel, subjective MF correlated with increased on-task activity and resting-state functional connectivity in the default mode network. These results indicate that subjective mental fatigue is not associated with altered activity in the brain motivation circuit but rather with hypoactivity in task-specific brain regions as well as relative increases of activity and connectivity in the default mode network during and after the task.

Brain reactivity to humorous films is affected by insomnia.

STUDY OBJECTIVES: Emotional reactivity to negative stimuli has been investigated in insomnia, but little is known about emotional reactivity to positive stimuli and its neural representation. METHODS: We used 3 Tesla functional magnetic resonance imaging (fMRI) to determine neural reactivity during the presentation of standardized short, 10- to 40-seconds, humorous films in patients with insomnia (n = 20, 18 females, aged 27.7 +/- 8.6 years) and age-matched individuals without insomnia (n = 20, 19 females, aged 26.7 +/- 7.0 years) and assessed humor ratings through a visual analog scale. Seed-based functional connectivity was analyzed for the left and right amygdalas (lAMYG and rAMYG, respectively) networks: group-level mixed-effects analysis (FLAME; FMRIB Software Library [FSL]) was used to compare amygdala connectivity maps between groups. RESULTS: fMRI seed-based analysis of the amygdala revealed stronger neural reactivity in patients with insomnia than in controls in several brain network clusters within the reward brain network, without humor rating differences between groups (p = 0.6). For lAMYG connectivity, cluster maxima were in the left caudate (Z = 3.88), left putamen (Z = 3.79), and left anterior cingulate gyrus (Z = 4.11), whereas for rAMYG connectivity, cluster maxima were in the left caudate (Z = 4.05), right insula (Z = 3.83), and left anterior cingulate gyrus (Z = 4.29). Cluster maxima of the rAMYG network were correlated with hyperarousal scores in patients with insomnia only. CONCLUSIONS: The presentation of humorous films leads to increased brain activity in the neural reward network for patients with insomnia compared with controls, related to hyperarousal features in patients with insomnia, in the absence of humor rating group differences. These novel findings may benefit insomnia treatment interventions. CLINICAL TRIAL: The Sleepless Brain: Neuroimaging Support for a Differential Diagnosis of Insomnia (SOMNET). ClinicalTrials.gov identifier: NCT02821234; https://clinicaltrials.gov/ct2/show/NCT02821234.

Effect of Distracting Background Speech in an Auditory Brain-Computer Interface.

Studies so far have analyzed the effect of distractor stimuli in different types of brain-computer interface (BCI). However, the effect of a background speech has not been studied using an auditory event-related potential (ERP-BCI), a convenient option when the visual path cannot be adopted by users. Thus, the aim of the present work is to examine the impact of a background speech on selection performance and user workload in auditory BCI systems. Eleven participants tested three conditions: (i) auditory BCI control condition, (ii) auditory BCI with a background speech to ignore (non-attentional condition), and (iii) auditory BCI while the user has to pay attention to the background speech (attentional condition). The results demonstrated that, despite no significant differences in performance, shared attention to auditory BCI and background speech required a higher cognitive workload. In addition, the P300 target stimuli in the non-attentional condition were significantly higher than those in the attentional condition for several channels. The non-attentional condition was the only condition that showed significant differences in the amplitude of the P300 between target and non-target stimuli. The present study indicates that background speech, especially when it is attended to, is an important interference that should be avoided while using an auditory BCI.

Insomnia does not affect heart rate changes when young adults watch humorous films: An exploratory study.

Emotional reactivity in insomnia is affected both subjectively and on a physiological level for negative emotional material, but little is known about reactions to positive stimuli. We here investigated whether in younger adult insomnia patients, presentation of short humorous films would lead to heart rate decreases during and after film viewing, as compared to heart rate changes when falling asleep. Investigating 20 participants with DSM-5-diagnosed insomnia and 18 participants without insomnia, we found that heart rate decreased when falling asleep, increased when watching humorous films and returned to normal values afterwards for all participants. Film-related heart rate increases were strongly related to humour ratings of the films. No differences were found between those with and without insomnia on subjective ratings of the films, film-related heart rate changes or when falling asleep. We conclude that the experience of positive daily life stimuli in younger adults is not affected by insomnia in our study, despite insomnia having a known more profound effect on negative stimuli. Future studies exploring insomnia-related autonomous nervous system responses combining different neurophysiological modalities should confirm our findings.

How sleep problems contribute to simulator sickness: Preliminary results from a realistic driving scenario.

Virtual reality and simulation tools enable us to assess daytime functioning in environments that simulate real life as close as possible. Simulator sickness, however, poses a problem in the application of these tools, and has been related to pre-existing health problems. How sleep problems contribute to simulator sickness has not yet been investigated. In the current study, 20 female chronic insomnia patients and 32 female age-matched controls drove in a driving simulator covering realistic city, country and highway scenes. Fifty percent of the insomnia patients as opposed to 12.5% of controls reported excessive simulator sickness leading to experiment withdrawal. In the remaining participants, patients with insomnia showed overall increased levels of oculomotor symptoms even before driving, while nausea symptoms further increased after driving. These results, as well as the realistic simulation paradigm developed, give more insight on how vestibular and oculomotor functions as well as interoceptive functions are affected in insomnia. Importantly, our results have direct implications for both the actual driving experience and the wider context of deploying simulation techniques to mimic real life functioning, in particular in those professions often exposed to sleep problems.

Functional brain network centrality is related to APOE genotype in cognitively normal elderly.

INTRODUCTION: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. METHODS: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. RESULTS: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. CONCLUSION: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.

Application of Machine Learning to Arterial Spin Labeling in Mild Cognitive Impairment and Alzheimer Disease.

Purpose To investigate whether multivariate pattern recognition analysis of arterial spin labeling (ASL) perfusion maps can be used for classification and single-subject prediction of patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) and subjects with subjective cognitive decline (SCD) after using the W score method to remove confounding effects of sex and age. Materials and Methods Pseudocontinuous 3.0-T ASL images were acquired in 100 patients with probable AD; 60 patients with MCI, of whom 12 remained stable, 12 were converted to a diagnosis of AD, and 36 had no follow-up; 100 subjects with SCD; and 26 healthy control subjects. The AD, MCI, and SCD groups were divided into a sex- and age-matched training set (n = 130) and an independent prediction set (n = 130). Standardized perfusion scores adjusted for age and sex (W scores) were computed per voxel for each participant. Training of a support vector machine classifier was performed with diagnostic status and perfusion maps. Discrimination maps were extracted and used for single-subject classification in the prediction set. Prediction performance was assessed with receiver operating characteristic (ROC) analysis to generate an area under the ROC curve (AUC) and sensitivity and specificity distribution. Results Single-subject diagnosis in the prediction set by using the discrimination maps yielded excellent performance for AD versus SCD (AUC, 0.96; P < .01), good performance for AD versus MCI (AUC, 0.89; P < .01), and poor performance for MCI versus SCD (AUC, 0.63; P = .06). Application of the AD versus SCD discrimination map for prediction of MCI subgroups resulted in good performance for patients with MCI diagnosis converted to AD versus subjects with SCD (AUC, 0.84; P < .01) and fair performance for patients with MCI diagnosis converted to AD versus those with stable MCI (AUC, 0.71; P > .05). Conclusion With automated methods, age- and sex-adjusted ASL perfusion maps can be used to classify and predict diagnosis of AD, conversion of MCI to AD, stable MCI, and SCD with good to excellent accuracy and AUC values. © RSNA, 2016.

Impact of APOE-ɛ4 and family history of dementia on gray matter atrophy in cognitively healthy middle-aged adults.

The apolipoprotein E ε4 allele (APOE4) and family history of dementia (FH) are well-known risk factors for the development of sporadic Alzheimer's disease. We assessed the effects of these risk factors on gray matter (GM) volume in 295 cognitively healthy middle-aged community-dwelling subjects. Voxel-based morphometry was used to study GM volume differences between high- and low-risk subjects, based on APOE4 carriership (n = 74), first-degree FH (n = 228), or both (n = 62). No significant results were found using a corrected p value. Using a more lenient threshold (p < 0.001 and minimum cluster size of 100 voxels), APOE4 carriers had reduced GM in the striatum compared to noncarriers. Subjects with FH had reduced GM in right precuneus compared to subjects without FH. Maternal and paternal FH provided similar atrophy patterns. APOE4 carriers with FH had GM reductions in bilateral insula compared to subjects with neither APOE4 nor FH. We conclude that a family history of dementia and APOE4 carriership are both associated with regional GM decreases in cognitively healthy middle-aged subjects, with differential effects on brain regions typically affected in Alzheimer's disease.

The bidirectional relation between emotional reactivity and sleep: From disruption to recovery.

Sleep disturbances are highly prevalent and greatly affect consecutive emotional reactivity, while sleep quality itself can be strongly affected by reactions to previous emotional events. In this review, we shed light on this bidirectional relation through examples of pathology: insomnia and bipolar disorder. We show that both experimental sleep deprivation and insomnia are related to increased emotional reactivity and increased amygdala activation upon emotional stimuli presentation, and that particularly Rapid Eye Movement (REM) sleep is important for emotional processing and reorganization of emotion-specific brain activity. Increased emotional reactivity affects REM sleep quality and sleep spindles, while REM sleep is particularly affected in insomnia, possibly related to condition-specific hyperarousal levels. Normal sleep onset deactivation of brain regions important for emotional processing (amygdala, anterior cingulate cortex (ACC)) is further affected in insomnia. In bipolar disorder, sleep disturbances are common in both symptomatic and nonsymptomatic phases. Both amygdala and ACC volume and function are affected in bipolar disorder, with the ACC showing phase-dependent resting state activity differences. Deficient Gamma-aminobutyric acid (GABA) GABA-ergic activity of this region might play a role in sleep disturbances and their influence on emotional reactivity, given the inhibitory role of GABA on brain activity during sleep and its deficiency in both bipolar disorder and insomnia. Promising findings of normalizing brain activity in both insomnia and bipolar disorder upon treatment may inspire a focus on treatment studies investigating the normalization of sleep, emotional reactivity, and their corresponding brain activity patterns. (PsycINFO Database Record

Gray matter network disruptions and amyloid beta in cognitively normal adults.

Gray matter networks are disrupted in Alzheimer's disease (AD). It is unclear when these disruptions start during the development of AD. Amyloid beta 1-42 (Aß42) is among the earliest changes in AD. We studied, in cognitively healthy adults, the relationship between Aß42 levels in cerebrospinal fluid (CSF) and single-subject cortical gray matter network measures. Single-subject gray matter networks were extracted from structural magnetic resonance imaging scans in a sample of cognitively healthy adults (N = 185; age range 39-79, mini-mental state examination >25, N = 12 showed abnormal Aß42 < 550 pg/mL). Degree, clustering coefficient, and path length were computed at whole brain level and for 90 anatomical areas. Associations between continuous Aß42 CSF levels and single-subject cortical gray matter network measures were tested. Smoothing splines were used to determine whether a linear or nonlinear relationship gave a better fit to the data. Lower Aß42 CSF levels were linearly associated at whole brain level with lower connectivity density, and nonlinearly with lower clustering values and higher path length values, which is indicative of a less-efficient network organization. These relationships were specific to medial temporal areas, precuneus, and the middle frontal gyrus (all p < 0.05). These results suggest that mostly within the normal spectrum of amyloid, lower Aß42 levels can be related to gray matter networks disruptions.

Information Flow Between Resting-State Networks.

UNLABELLED: The resting brain dynamics self-organize into a finite number of correlated patterns known as resting-state networks (RSNs). It is well known that techniques such as independent component analysis can separate the brain activity at rest to provide such RSNs, but the specific pattern of interaction between RSNs is not yet fully understood. To this aim, we propose here a novel method to compute the information flow (IF) between different RSNs from resting-state magnetic resonance imaging. After hemodynamic response function blind deconvolution of all voxel signals, and under the hypothesis that RSNs define regions of interest, our method first uses principal component analysis to reduce dimensionality in each RSN to next compute IF (estimated here in terms of transfer entropy) between the different RSNs by systematically increasing k (the number of principal components used in the calculation). When k=1, this method is equivalent to computing IF using the average of all voxel activities in each RSN. For k≥1, our method calculates the k multivariate IF between the different RSNs. We find that the average IF among RSNs is dimension dependent, increasing from k=1 (i.e., the average voxel activity) up to a maximum occurring at k=5 and to finally decay to zero for k≥10. This suggests that a small number of components (close to five) is sufficient to describe the IF pattern between RSNs. Our method--addressing differences in IF between RSNs for any generic data--can be used for group comparison in health or disease. To illustrate this, we have calculated the inter-RSN IF in a data set of Alzheimer's disease (AD) to find that the most significant differences between AD and controls occurred for k=2, in addition to AD showing increased IF w.r.t. CONTROLS: The spatial localization of the k=2 component, within RSNs, allows the characterization of IF differences between AD and controls.

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown.

Reading networks in children with dyslexia compared to children with ocular motility disturbances revealed by fMRI.

Key PointsDyslexia is a neurological disorder with a genetic origin, but the underlying biological and cognitive causes are still being investigated.This study compares the brain activation pattern while reading in Spanish, a semitransparent language, in three groups of children: typically developing readers, dyslexic readers and readers with functional monocular vision.Based on our results Dyslexia would be a neurological disorder not related to vision impairments and would require a multidisciplinary treatment based on improving phonological awareness and language development. Developmental dyslexia is a neurological disorder the underlying biological and cognitive causes of which are still being investigated, a key point, because the findings will determine the best therapeutic approach to use. Using functional magnetic resonance imaging, we studied the brain activation pattern while reading in the language-related cortical areas from the two reading routes, phonological and orthographic, and the strength of their association with reading scores in 66 Spanish-speaking children aged 9-12 years divided into three groups: typically developing readers (controls), dyslexic readers and readers with monocular vision due to ocular motility disorders but with normal reading development, to assess whether (or not) the neuronal network for reading in children with dyslexia has similarities with that in children with impaired binocular vision due to ocular motility disorders. We found that Spanish-speaking children with dyslexia have a brain circuit for reading that differs from that in children with monocular vision. Individuals with dyslexia tend to hypoactivate some of the language-related areas in the left hemisphere engaged by the phonological route, especially the visual word form area and left Wernicke's area, and try to compensate this deficit by activating language-related areas related to the orthographic route, such as the anterior part of the visual word form area and the posterior part of both middle temporal gyri. That is, they seem to compensate for impairment in the phonological route through orthographic routes of both hemispheres. Our results suggest that ocular motility disturbances do not play a causal role in dyslexia. Dyslexia seems to be a neurological disorder that is unrelated to vision impairments and requires early recognition and multidisciplinary treatment, based on improving phonological awareness and language development, to achieve the best possible outcome.

Differentiation of edema and glioma infiltration: proposal of a DTI-based probability map.

Conflicting results on differentiating edema and glioma by diffusion tensor imaging (DTI) are possibly attributable to dissimilar spatial distribution of the lesions. Combining DTI-parameters and enhanced registration might improve prediction. Regions of edema surrounding 22 metastases were compared to tumor-infiltrated regions from WHO grade 2 (12), 3 (10) and 4 (18) gliomas. DTI data was co-registered using Tract Based Spatial Statistics (TBSS), to measure Fractional Anisotropy (FA) and Mean Diffusivity (MD) for white matter only, and relative changes compared to matching reference regions (dFA and dMD). A two-factor principal component analysis (PCA) on metastasis and grade 2 glioma was performed to explore a possible differentiating combined factor. Edema demonstrated equal MD and higher FA compared to grade 2 and 3 glioma (P < 0.001), but did not differ from glioblastoma. Differences were non-significant when corrected for spatial distribution, since reference regions differed strongly (P < 0.001). The second component of the PCA (PCA-C2) did differentiate edema and low-grade tumor (sensitivity 91.7%, specificity 86.4%). PCA-C2 scores were plotted voxel-wise as a probability-map, discerning distinct areas of presumed edema or tumor infiltration. Correction of spatial dependency appears essential when differentiating glioma from edema. A tumor-infiltration probability-map is presented, based on supplementary information of multiple DTI parameters and spatial normalization.

Brain functional connectivity changes in children that differ in impulsivity temperamental trait.

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior.

Amyloid and its association with default network integrity in Alzheimer's disease.

The purpose of this study was to investigate the association between functional connectivity and ß-amyloid depositions in the default mode network (DMN) in Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and healthy elderly. Twenty-five patients with AD, 12 patients with MCI, and 18 healthy controls were included in the study. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in the DMN. In parallel, amyloid burden was measured in the same subjects using positron emission tomography with carbon-11-labeled Pittsburgh Compound-B as amyloid tracer. Functional connectivity of the DMN and amyloid deposition within the DMN were not associated across all subjects or within diagnostic groups. Longitudinal studies are needed to examine if amyloid depositions precede aberrant functional connectivity in the DMN.

The caudate: a key node in the neuronal network imbalance of insomnia?

Insomnia is prevalent, severe and partially heritable. Unfortunately, its neuronal correlates remain enigmatic, hampering the development of mechanistic models and rational treatments. Consistently reported impairments concern fragmented sleep, hyper-arousal and executive dysfunction. Because fronto-striatal networks could well play a role in sleep, arousal regulation and executive functioning, the present series of studies used an executive task to evaluate fronto-striatal functioning in disturbed sleep. Patients with insomnia showed reduced recruitment of the head of the left caudate nucleus during executive functioning, which was not secondary to altered performance or baseline perfusion. Individual differences in caudate recruitment were associated with hyper-arousal severity. Seed-based functional connectivity analysis suggested that attenuated input from a projecting orbitofrontal area with reduced grey matter density contributes to altered caudate recruitment in patients with insomnia. Attenuated caudate recruitment persisted after successful treatment of insomnia, warranting evaluation as a potential vulnerability trait. A similar selective reduction in caudate recruitment could be elicited in participants without sleep complaints by slow-wave sleep fragmentation, providing a model to facilitate investigation of the causes and consequences of insomnia.