Cortical thinning explains changes in sleep slow waves during adulthood.

Sleep slow waves (SWs) change considerably throughout normal aging. In humans, SWs are generated and propagate on a structural backbone of highly interconnected cortical regions that form most of the default mode network, such as the insula, cingulate cortices, temporal lobe, parietal lobe, and medial frontal lobe. Regions in this network undergo cortical thinning and breakdown in structural and functional connectivity over the course of normal aging. In this study, we investigated how changes in cortical thickness (CT), a measure of gray matter integrity, are involved in modifications of sleep SWs during adulthood in humans. Thirty young (mean age = 23.49 years; SD = 2.79) and 33 older (mean age = 60.35 years; SD = 5.71) healthy subjects underwent a nocturnal polysomnography and T1 MRI. We show that, when controlling for age, higher SW density (nb/min of nonrapid eye movement sleep) was associated with higher CT in cortical regions involved in SW generation surrounding the lateral fissure (insula, superior temporal, parietal, middle frontal), whereas higher SW amplitude was associated with higher CT in middle frontal, medial prefrontal, and medial posterior regions. Mediation analyses demonstrated that thinning in a network of cortical regions involved in SW generation and propagation, but also in cognitive functions, explained the age-related decrease in SW density and amplitude. Altogether, our results suggest that microstructural degradation of specific cortical regions compromise SW generation and propagation in older subjects, critically contributing to age-related changes in SW oscillations.

α-Cationic Arsines: Synthesis, Structure, Reactivity, and Applications.

A series of structurally differentiated cationic arsines containing imidazolium, cyclopropenium, formamidinium, and pyridinium substituents have been synthesized through short and scalable routes. Evaluation of the donor properties of these compounds by IR spectroscopy and DFT calculations reveals similar σ-electron-releasing abilities for all of them; however, their π-acceptor properties are strongly influenced by the nature of the positively charged group. We describe the coordination chemistry of the newly prepared α-cationic arsines toward different metal centers and their reactivity in the presence of strong oxidants to afford cationic As(V) species. Their unique electronic properties have been exploited in Pt(II) catalysis to develop a new catalyst with remarkable activity in the cycloisomerization of enynes to trisubstituted cyclopropanes. To the best of our knowledge, this is the first report on the use of α-cationic arsine ligands in catalysis.

Bis(cyclopropenium)phosphines: Synthesis, Reactivity, and Applications.

A straightforward route for the preparation of a set of bis(cyclopropenium)-substituted phosphines is reported. Due to their dicationic nature, these ligands depict an excellent π-acceptor character. The effect of the ligand substituent pattern on the catalytic activity of the metal complexes thereof derived is also studied. Whereas sterically demanding biaryl groups directly attached to the phosphorus atom seem to facilitate elementary steps such as the product release from the catalyst, long chain dialkylamino groups on the cyclopropenium units maximize the catalysts solubility and, thus, allow the use of typical apolar solvents such as toluene. Importantly, all new ligands prepared can be easily handled in air. Finally, the impact of the newly prepared dicationic phosphines in hydroarylation reactions is demonstrated. In particular, their use in the synthesis of several naphtho[1,2-b]furanes and naturally occurring naphthalene derivatives such as Calanquinone C is reported.

Reversible, photoinduced activation of P4 by low-coordinate main group compounds.

Two unique systems based on low-coordinate main group elements that activate P4 are shown to quantitatively release the phosphorus cage upon short exposure to UV light. This reactivity marks the first reversible reactivity of P4, and the germanium system can be cycled 5 times without appreciable loss in activity. Theoretical calculations reveal that the LUMO is antibonding with respect to the main group element-phosphorus bonds and bonding with respect to reforming the P4 tetrahedron, providing a rationale for this unprecedented activity, and suggesting that the process is tunable based on the substituents.

Sleep spindles and rapid eye movement sleep as predictors of next morning cognitive performance in healthy middle-aged and older participants.

Spindles and slow waves are hallmarks of non-rapid eye movement sleep. Both these oscillations are markers of neuronal plasticity, and play a role in memory and cognition. Normal ageing is associated with spindle and slow wave decline and cognitive changes. The present study aimed to assess whether spindle and slow wave characteristics during a baseline night predict cognitive performance in healthy older adults the next morning. Specifically, we examined performance on tasks measuring selective and sustained visual attention, declarative verbal memory, working memory and verbal fluency. Fifty-eight healthy middle-aged and older adults (aged 50-91 years) without sleep disorders underwent baseline polysomnographic sleep recording followed by neuropsychological assessment the next morning. Spindles and slow waves were detected automatically on artefact-free non-rapid eye movement sleep electroencephalogram. All-night stage N2 spindle density (no./min) and mean frequency (Hz) and all-night non-rapid eye movement sleep slow wave density (no./min) and mean slope (µV/s) were analysed. Pearson's correlations were performed between spindles, slow waves, polysomnography and cognitive performance. Higher spindle density predicted better performance on verbal learning, visual attention and verbal fluency, whereas spindle frequency and slow wave density or slope predicted fewer cognitive performance variables. In addition, rapid eye movement sleep duration was associated with better verbal learning potential. These results suggest that spindle density is a marker of cognitive functioning in older adults and may reflect neuroanatomic integrity. Rapid eye movement sleep may be a marker of age-related changes in acetylcholine transmission, which plays a role in new information encoding.

Addressing the chemical sorcery of "GaI": benefits of solid-state analysis aiding in the synthesis of P→Ga coordination compounds.

The differing structures and reactivities of "GaI" samples prepared with different reaction times have been investigated in detail. Analysis by FT-Raman spectroscopy, powder X-ray diffraction, (71)Ga solid-state NMR spectroscopy, and (127)I nuclear quadrupole resonance (NQR) provides concrete evidence for the structure of each "GaI" sample prepared. These techniques are widely accessible and can be implemented quickly and easily to identify the nature of the "GaI" in hand. The "GaI" prepared from exhaustive reaction times (100 min) is shown to possess Ga2I3 and an overall formula of [Ga(0)]2[Ga(+)]2[Ga2I6(2-)], while the "GaI" prepared with the shortest reaction time (40 min) contains GaI2 and has the overall formula [Ga(0)]2[Ga(+)][GaI4(-)]. Intermediate "GaI" samples were consistently shown to be fractionally composed of each of these two preceding formulations and no other distinguishable phases. These "GaI" phases were then shown to give unique products upon reactions with the anionic bis(phosphino)borate ligand class. The reaction of the early-phase "GaI" gives rise to a unique phosphine Ga(II) dimeric coordination compound (3), which was isolated reproducibly in 48% yield and convincingly characterized. A base-stabilized GaI→GaI3 fragment (4) was also isolated using the late-phase "GaI" and characterized by multinuclear NMR spectroscopy and X-ray crystallography. These compounds can be considered unique examples of low-oxidation-state P→Ga coordination compounds and possess relatively long Ga-P bond lengths in the solid-state structures. The anionic borate backbone therefore results in interesting architectures about gallium that have not been observed with neutral phosphines.

Synthesis and onwards coordination of an As(I) centered zwitterion.

The bis(phosphino)borate ligand class is used as an anionic anchor to stabilize reactive, low coordinate arsenic centers. The neutral, zwitterionic As(I) species, 2, is formed very cleanly, and isolated in good yields using cyclohexene as a halogen scavenger. The uniqueness of this heterocyclic As(I) compound is on display with the coordination to Group 6 metal centers, (2 M(CO)5; M = Cr, Mo, W). The arsenic-metal bond lengths are longer than the related AsPh3 complexes suggesting that compound 2 is a weak sigma donor. The metal complexes reveal a trigonal pyramidal arsenic atom, which provides the first experimental evidence for the presence of two "lone pairs" of electrons on the As(I) center. When more flexible and more electron-donating isopropyl substituents were used, an intermediate (compound 5) in the formation of low coordinate pnictogen compounds was crystallographically characterized. This structure, formally a base-stabilized dichloroarsenium cation, provides an alternative mechanistic proposal to the one described in the literature.

Synthesis of zwitterionic triphosphenium transition metal complexes: a boron atom makes the difference.

A collection of zwitterionic phosphanide metal carbonyl coordination complexes has been synthesized and fully characterized, representing the first isolated series of metal complexes for the triphosphenium family of compounds. The dicoordinate phosphorus atom of the zwitterion is formally in the +1 oxidation state and can coordinate to one metal, 2M (M = Cr, Mo, W) and 2Fe, or two metals, a Co2(CO)6 fragment 4, depending on the starting reagents. All complexes have been isolated in greater than 80% yield, and structures were confirmed crystallographically. Metrical parameters are consistent with 1 being a weak donor and results in long metal-phosphorus bonds being observed in all cases. Unique bimetallic structures, 3M (M = Cr, Mo, W), consisting of a M(CO)5 fragment on phosphorus and a piano-stool M(CO)3 fragment on a boron phenyl group have been identified in the (31)P{(1)H} NMR spectra and confirmed using X-ray diffraction studies. Use of the borate backbone in 1, which renders the molecule zwitterionic, proves to be a determining factor in whether these metal complexes will form; the halide salt of a cationic triphosphenium ion, 6[Br], shows no evidence for formation of the analogous metal complexes by (31)P{(1)H} NMR spectroscopy, and tetraphenylborate salts, 6[BPh4] and 7[BPh4], produce complexes that are unstable.

Photoinduced carbene generation from diazirine modified task specific phosphonium salts to prepare robust hydrophobic coatings.

3-Aryl-3-(trifluormethyl)diazirine functionalized highly fluorinated phosphonium salts (HFPS) were synthesized, characterized, and utilized as photoinduced carbene precursors for covalent attachment of the HFPS onto cotton/paper to impart hydrophobicity to these surfaces. Irradiation of cotton and paper, as proof of concept substrates, treated with the diazirine-HFPS leads to robust hydrophobic cotton and paper surfaces with antiwetting properties, whereas the corresponding control samples absorb water readily. The contact angles of water were determined to be 139° and 137° for cotton and paper, respectively. In contrast, water placed on the untreated or the control samples (those treated with the diazirine-HFPS but not irradiated) is simply absorbed into the surface. Additionaly, the chemically grafted hydrophobic coating showed high durability toward wash cycles and sonication in organic solvents. Because of the mode of activation to covalently tether the hydrophobic coating, it is amenable to photopatterning, which was demonstrated macroscopically.

Homoleptic pnictogen-chalcogen coordination complexes.

The synthesis and structural characterization of dicationic selenium and tellurium analogues of the carbodiphosphorane and triphosphenium families of compounds are reported. These complexes, [Ch(dppe)][OTf](2) [Ch = Se, Te; dppe = 1,2-bis(diphenylphosphino)ethane; OTf = trifluoromethanesulfonate], are formed using [Ch](2+) reagents via a ligand-exchange protocol and represent extremely rare examples of homoleptic pnictogen → chalcogen coordination complexes. The corresponding arsenic compounds were also prepared, [Ch(dpAse)][OTf](2) [Ch = Se, Te; dpAse = 1,2-bis(diphenylarsino)ethane], exhibiting the first instance of an arsenic → chalcogen dative bond. The electronic structures of these unique compounds were determined and compared to previously reported chalcogen dications.

Accessing the coordination chemistry of phosphorus(I) zwitterions.

Go for the gold! Incorporating a borate anion into the backbone of a triphosphenium cation produces a unique zwitterionic phosphanide that can coordinate to one or two {AuCl} fragments depending on the steric bulk of the ligand (see picture; Au yellow, P purple, Cl green). Computational investigations show that in this µ-type ligand, the phosphorus atom behaves only as a σ,π donor.

Follow-up CT Imaging in Patients With Traumatic Brain Injury in Zimbabwe.

PURPOSE: To assess the type and degree of neurological complications in patients with traumatic brain injury (TBI) who presented with an initial typical baseline computed tomography (CT) brain scan and to assess the time in which neurological complications developed. METHODS: A retrospective cross-sectional quantitative research design was conducted in whichCT radiology reports of 85 adult patients with TBI and typical baseline CT scans were analyzed during a 2-year period. The evolution of different types of neurological pathology diagnosed on follow-up CT brain imaging in these patients was recorded and analyzed. RESULTS: The results showed that 36% of patients (n = 31) presented with atypical neuroradiological findings on follow-up CT imaging. Subdural hematoma was diagnosed in 19% (n = 16), intracerebral hematoma in 8% (n = 7), subarachnoid hematoma in 6% (n = 5), pneumocephalus in 2% (n = 2), and epidural hematoma in 1% (n = 1). The average times elapsed between the traumatic event and acquisition of the baseline CT brain scan and follow-up CT were 8 and 18 hours, respectively. DISCUSSION: The most common causal mechanism of trauma in this study was motor vehicle collisions; an increase in motor vehicle collisions might have resulted in many vulnerable road users on poor road infrastructure and communities living in the vicinity of such roads. The severity of neurological status of patients might be associated with a higher likelihood of detecting intracranial pathology on follow-up CT brain imaging. Follow-up CT brain imaging findings have a role in confirming or excluding late neurological complications preceded by a typical baseline CT brain scan. CONCLUSION: Follow-up CT brain imaging performed at 10 hours after the typical baseline CT scan was of value in detecting the evolution of intracranial neurological pathology and resulted in a change in neurological management in one-third of patients.

Are age and sex effects on sleep slow waves only a matter of electroencephalogram amplitude?

Aging is associated with reduced slow wave (SW) density (number SW/min in nonrapid-eye movement sleep) and amplitude. It has been proposed that an age-related decrease in SW density may be due to a reduction in electroencephalogram (EEG) amplitude instead of a decline in the capacity to generate SW. Here, we propose a data-driven approach to adapt SW amplitude criteria to age and sex. We predicted that the adapted criteria would reduce age and sex differences in SW density and SW characteristics but would not abolish them. A total of 284 healthy younger and older adults participated in one night of sleep EEG recording. We defined age- and sex-adapted SW criteria in a first cohort of younger (n = 97) and older (n = 110) individuals using a signal-to-noise ratio approach. We then used these age- and sex-specific criteria in an independent second cohort (n = 77, 38 younger and 39 older adults) to evaluate age and sex differences on SW density and SW characteristics. After adapting SW amplitude criteria, we showed maintenance of an age-related difference for SW density whereas the sex-related difference vanished. Indeed, older adults produced less SW compared with younger adults. Specifically, the adapted SW amplitude criteria increased the probability of occurrence of low amplitude SW (<80 µV) for older men especially. Our results thereby confirm an age-related decline in SW generation rather than an artifact in the detection amplitude criteria. As for the SW characteristics, the age- and sex-adapted criteria display reproducible effects across the two independent cohorts suggesting a more reliable inventory of the SW.

Sleeping at the switch.

Sleep slow waves are studied for their role in brain plasticity, homeostatic regulation, and their changes during aging. Here, we address the possibility that two types of slow waves co-exist in humans. Thirty young and 29 older adults underwent a night of polysomnographic recordings. Using the transition frequency, slow waves with a slow transition (slow switchers) and those with a fast transition (fast switchers) were discovered. Slow switchers had a high electroencephalography (EEG) connectivity along their depolarization transition while fast switchers had a lower connectivity dynamics and dissipated faster during the night. Aging was associated with lower temporal dissipation of sleep pressure in slow and fast switchers and lower EEG connectivity at the microscale of the oscillations, suggesting a decreased flexibility in the connectivity network of older individuals. Our findings show that two different types of slow waves with possible distinct underlying functions coexist in the slow wave spectrum.

EEG connectivity across sleep cycles and age.

STUDY OBJECTIVES: In young adults, sleep is associated with important changes in cerebral connectivity during the first cycle of non-rapid eye movement (NREM) sleep. Our study aimed to evaluate how electroencephalography (EEG) connectivity during sleep differs between young and older individuals, and across the sleep cycles. METHODS: We used imaginary coherence to estimate EEG connectivity during NREM and rapid eye movement (REM) sleep in 30 young (14 women; 20-30 years) and 29 older (18 women; 50-70 years) individuals. We also explored the association between coherence and cognitive measures. RESULTS: Older individuals showed lower EEG connectivity in stage N2 but higher connectivity in REM and stage N3 compared to the younger cohort. Age-related differences in N3 were driven by the first sleep cycle. EEG connectivity was lower in REM than N3, especially in younger individuals. Exploratory analyses, controlling for the effects of age, indicated that higher EEG connectivity in delta during N2 was associated with higher processing speed, whereas, during REM sleep, lower EEG connectivity in delta and sigma was associated with higher verbal memory performance and a higher global averaged intelligence quotient score. CONCLUSION: Our results indicated that age modifies sleep EEG connectivity but the direction and the magnitude of these effects differ between sleep stages and cycles. Results in N3 and REM point to a reduced ability of the older brains to disconnect as compared to the younger ones. Our results also support the notion that cerebral functional connectivity during sleep may be associated with cognitive functions.

Age-related cortical signatures of human sleep electroencephalography.

Accumulating evidence demonstrates a direct relationship between impaired neural integrity and disrupted sleep physiology in normal and pathological aging. However, previous work has focus almost exclusively on nonrapid eye movement sleep electroencephalography as a proxy of cortical integrity with aging. Whether this relationship holds true for rapid eye movement sleep electroencephalography is unknown. Our results show that age-related reduction in low-frequency delta activity during both rapid eye movement and nonrapid eye movement sleep was statistically mediated by the thinning of the medial frontal and anterior cingulate cortices. These findings (1) support the potential role of the medial frontal and cingulate cortices, major hubs of the human brain, in synchronizing neuronal assemblies during sleep, and (2) suggest that, with age, a reduction in cortical integrity within this frontal network mediates the loss of delta power during sleep. Further work will determine whether cortical thinning and delta loss may interact and contribute to cognitive decline with aging.

Sleep-Wake Cycle in Young and Older Mice.

Sleep plays a key role in multiple cognitive functions and sleep pattern changes with aging. Human studies revealed that aging decreases sleep efficiency and reduces the total sleep time, the time spent in slow-wave sleep (SWS), and the delta power (1-4 Hz) during sleep; however, some studies of sleep and aging in mice reported opposing results. The aim of our work is to estimate how features of sleep-wake state in mice during aging could correspond to age-dependent changes observed in human. In this study, we investigated the sleep/wake cycle in young (3 months old) and older (12 months old) C57BL/6 mice using local-field potentials (LFPs). We found that older adult mice sleep more than young ones but only during the dark phase of sleep-wake cycle. Sleep fragmentation and sleep during the active phase (dark phase of cycle), homologous to naps, were higher in older mice. Older mice show a higher delta power in frontal cortex, which was accompanied with similar trend for age differences in slow wave density. We also investigated regional specificity of sleep-wake electrographic activities and found that globally posterior regions of the cortex show more rapid eye movement (REM) sleep whereas somatosensory cortex displays more often SWS patterns. Our results indicate that the effects of aging on the sleep-wake activities in mice occur mainly during the dark phase and the electrode location strongly influence the state detection. Despite some differences in sleep-wake cycle during aging between human and mice, some features of mice sleep share similarity with human sleep during aging.

The association between white matter and sleep spindles differs in young and older individuals.

Study Objectives: Sleep is a reliable indicator of cognitive health in older individuals. Sleep spindles (SS) are non-rapid eye movement (NREM) sleep oscillations implicated in sleep-dependent learning. Their generation imply a complex activation of the thalamo-cortico-thalamic loop. Since SS require neuronal synchrony, the integrity of the white matter (WM) underlying these connections is of major importance. During aging, both SS and WM undergo important changes. The goal of this study was to investigate whether WM integrity could predict the age-related reductions in SS characteristics. Methods: Thirty young and 31 older participants underwent a night of polysomnographic recording and a 3T magnetic resonance imaging acquisition including a diffusion sequence. SS were detected in NREM sleep and EEG spectral analysis was performed for the sigma frequency band. WM diffusion metrics were computed in a voxelwise design of analysis. Results: Compared to young participants, older individuals showed lower SS density, amplitude, and sigma power. Diffusion metrics were correlated with SS amplitude and sigma power in tracts connecting the thalamus to the frontal cortex for the young but not for the older group, suggesting a moderation effect. Moderation analyses showed that diffusion metrics explained between 14% and 39% of SS amplitude and sigma power variance in the young participants only. Conclusion: Our results indicate that WM underlying the thalamo-cortico-thalamic loop predicts SS characteristics in young individuals, but does not explain age-related changes in SS. Other neurophysiological factors could better explain the effect of age on SS characteristics.

Spatial Organization of Epigenomes.

The role of genome architecture in transcription regulation has become the focus of an increasing number of studies over the past decade. Chromatin organization can have a significant impact on gene expression by promoting or restricting the physical proximity between regulatory DNA elements. Given that any change in chromatin state has the potential to alter DNA folding and the proximity between control elements, the spatial organization of chromatin is inherently linked to its molecular composition. In this review, we explore how modulators of chromatin state and organization might keep gene expression in check. We discuss recent findings and present some of the less well-studied aspects of spatial genome organization such as chromatin dynamics and regulation by non-coding RNAs.

A time-frequency analysis of the dynamics of cortical networks of sleep spindles from MEG-EEG recordings.

Sleep spindles are a hallmark of NREM sleep. They result from a widespread thalamo-cortical loop and involve synchronous cortical networks that are still poorly understood. We investigated whether brain activity during spindles can be characterized by specific patterns of functional connectivity among cortical generators. For that purpose, we developed a wavelet-based approach aimed at imaging the synchronous oscillatory cortical networks from simultaneous MEG-EEG recordings. First, we detected spindles on the EEG and extracted the corresponding frequency-locked MEG activity under the form of an analytic ridge signal in the time-frequency plane (Zerouali et al., 2013). Secondly, we performed source reconstruction of the ridge signal within the Maximum Entropy on the Mean framework (Amblard et al., 2004), yielding a robust estimate of the cortical sources producing observed oscillations. Lastly, we quantified functional connectivity among cortical sources using phase-locking values. The main innovations of this methodology are (1) to reveal the dynamic behavior of functional networks resolved in the time-frequency plane and (2) to characterize functional connectivity among MEG sources through phase interactions. We showed, for the first time, that the switch from fast to slow oscillatory mode during sleep spindles is required for the emergence of specific patterns of connectivity. Moreover, we show that earlier synchrony during spindles was associated with mainly intra-hemispheric connectivity whereas later synchrony was associated with global long-range connectivity. We propose that our methodology can be a valuable tool for studying the connectivity underlying neural processes involving sleep spindles, such as memory, plasticity or aging.