Spindle Frequency Research Articles

CAD/CAM interfaced algorithm reduces cutting force, roughness, and machining time in free-form milling

A ball-end cutting tool is usually chosen to mill free-form surfaces in finishing operations. The cutting speed, which is calculated considering the nominal tool diameter, reduces along the tool path, according to tool-surface contact and the effective tool diameter. This brings several drawbacks to the manufacturing process. The current work presents a new algorithm to optimize CNC codes for milling free-form surfaces by parametrizing and adjusting the spindle frequency and the feed rate, considering the tool-surface contact. The proposed algorithm introduces new values for spindle frequency (S) and for feed rate (F) at each line of the CNC code, according to the surface topography. Machining experiments show that the proposed algorithm can reduce the milling time up to 40%, as well as reduce the machining force up to 21%, compared to the ordinary CNC codes. By keeping the cutting speed and feed rate constant, the surface roughness was improved—confirmed by ANOVA analysis—due to the increased shear mechanism rather than ploughing, especially in areas where the effective tool diameter is smaller.

Sleep spindles are resilient to extensive white matter deterioration

Sleep spindles are an essential part of non-rapid eye movement sleep, notably involved in sleep consolidation, cognition, learning and memory. These oscillatory waves depend on an interaction loop between the thalamus and the cortex, which relies on a structural backbone of thalamo-cortical white matter tracts. It is still largely unknown if the brain can properly produce sleep spindles when it underwent extensive white matter deterioration in these tracts, and we hypothesized that it would affect sleep spindle generation and morphology. We tested this hypothesis with chronic moderate to severe traumatic brain injury (n = 23; 30.5 ± 11.1 years old; 17 m/6f), a unique human model of extensive white matter deterioration, and a healthy control group (n = 27; 30.3 ± 13.4 years old; 21m/6f). Sleep spindles were analysed on a full night of polysomnography over the frontal, central and parietal brain regions, and we measured their density, morphology and sigma-band power. White matter deterioration was quantified using diffusion-weighted MRI, with which we performed both whole-brain voxel-wise analysis (Tract-Based Spatial Statistics) and probabilistic tractography (with High Angular Resolution Diffusion Imaging) to target the thalamo-cortical tracts. Group differences were assessed for all variables and correlations were performed separately in each group, corrected for age and multiple comparisons. Surprisingly, although extensive white matter damage across the brain including all thalamo-cortical tracts was evident in the brain-injured group, sleep spindles remained completely undisrupted when compared to a healthy control group. In addition, almost all sleep spindle characteristics were not associated with the degree of white matter deterioration in the brain-injured group, except that more white matter deterioration correlated with lower spindle frequency over the frontal regions. This study highlights the resilience of sleep spindles to the deterioration of all white matter tracts critical to their existence, as they conserve normal density during non-rapid eye movement sleep with mostly unaltered morphology. We show that even with such a severe traumatic event, the brain has the ability to adapt or to withstand alterations in order to conserve normal sleep spindles.

Timely chatter identification for robotic drilling using a local maximum synchrosqueezing-based method

Induced by flexibility of the industrial robot, cutting tool or the workpiece, chatter in robotic machining process has detrimental effects on the surface quality, tool life and machining productivity. Consequently, accurate detection and timely suppression for such undesirable vibration is desperately needed to achieve high performance robotic machining. This paper presents a novel approach combining the notch filter and local maximum synchrosqueezing transform for the timely chatter identification in robotic drilling. The proposed approach is accomplished through the following steps. In the first step, the optimal matrix notch filter is designed to eliminate the interference of the spindle frequency and corresponding harmonic components to the measured acceleration signal. Subsequently, the high-resolution time–frequency information of the non-stationary filtered acceleration signal is acquired by employing local maximum synchrosqueezing transform (LMSST). On this basis, the filtered acceleration signal is divided into a finite number of equal-width frequency bands, and the corresponding sub-signal for each frequency band is obtained by summing the corresponding coefficient of the LMSST. Finally, to accurately depict the non-uniformity of energy distribution during the chatter incubation process, the statistical energy entropy is calculated and utilized as the indicator to detect chatter online. The effectiveness of the proposed approach is validated by a large number of robot drilling experiments with different cutting tools, workpiece materials and machining parameters. The results show that the presented local maximum synchrosqueezing-based approach can effectively recognize the chatter at an early stage during its incubation and development process.

Coupling and Decoupling between Brain and Body Oscillations

Cross frequency coupling is used to study the cross talk between brain oscillations. In this paper we focus on a special type of frequency coupling between brain and body oscillations, which is reflected by the numerical ratio (r) between two frequencies (m and n; n > m). This approach is motivated by theoretical considerations, indicating that during alert wakefulness brain-body oscillations form a coupled hierarchy of frequencies with integer relationships that are binary multiples (r = n:m = 1:2, 1:4, 1:8…..). During sleep we expect an irrational relationship (r = n/m = irrational number) between brain and body oscillations that reflects decoupling. We analyzed alpha frequency, heart rate, breathing frequency during performance of a memory tasks and in addition spindle frequency from data collected by the SIESTA sleep research group. As predicted, our results show a binary multiple frequency relationship between alpha, heart rate and breathing frequency during task performance but an irrational relationship between spindle frequency, heart rate and breathing frequency during sleep.

Age-related differences and sexual dimorphism in canine sleep spindles

Non-REM bursts of activity in the sigma range (9–16 Hz) typical of sleep spindles predict learning in dogs, similar to humans and rats. Little is known, however, about the age-related changes in amplitude, density (spindles/minute) and frequency (waves/second) of canine spindles. We investigated a large sample (N = 155) of intact and neutered pet dogs of both sexes, varying in breed and age, searching for spindles in segments of non-REM sleep. We recorded EEG from both a frontal midline electrode (Fz) and a central midline electrode (Cz) in 55.5% of the dogs, in the remaining animals only the Fz electrode was active (bipolar derivation). A similar topography was observed for fast (≥13 Hz) spindle occurrence as in humans (fast spindle number, density on Cz > Fz). For fast spindles, density was higher in females, and increased with age. These effects were more pronounced among intact animals and on Fz. Slow spindle density declined and fast spindle frequency increased with age on Cz, while on Fz age-related amplitude decline was observed. The frequency of fast spindles on Fz and slow spindles on Cz was linked to both sex and neutering, suggesting modulation by sexual hormones. Intact females displayed higher frequencies than males and neutered females. Our findings support the argument that sigma bursts in the canine non-REM sleep are analogous to human sleep spindles, and suggest that slow and fast spindles display different trajectories related to age, of which an increase in frontal fast spindles is unique to dogs.

Dynamics of sleep oscillations is coupled to brain temperature on multiple scales.

Sleep spindle frequency positively, duration negatively correlates with brain temperature. Local heating of the thalamus produces similar effects in the heated area. Thalamic network model corroborates temperature dependence of sleep spindle frequency. Brain temperature shows spontaneous microfluctuations during both anesthesia and natural sleep. Larger fluctuations are associated with epochs of REM sleep. Smaller fluctuations correspond to the alteration of spindling and delta epochs of infra-slow oscillation. Every form of neural activity depends on temperature, yet its relationship to brain rhythms is poorly understood. In this work we examined how sleep spindles are influenced by changing brain temperatures and how brain temperature is influenced by sleep oscillations. We employed a novel thermoelectrode designed for measuring temperature while recording neural activity. We found that spindle frequency is positively correlated and duration negatively correlated with brain temperature. Local heating of the thalamus replicated the temperature dependence of spindle parameters in the heated area only, suggesting biophysical rather than global modulatory mechanisms, a finding also supported by a thalamic network model. Finally, we show that switches between oscillatory states also influence brain temperature on a shorter and smaller scale. Epochs of paradoxical sleep as well as the infra-slow oscillation were associated with brain temperature fluctuations below 0.2°C. Our results highlight that brain temperature is massively intertwined with sleep oscillations on various time scales.

Association of inattention with slow-spindle density in sleep EEG of children with attention deficit-hyperactivity disorder

ObjectiveWe evaluated the power of slow sleep spindles during sleep stage 2 to clarify their relationship with executive function, especially with attention, in children with attention deficit-hyperactivity disorder (ADHD). MethodsSubjects were 21 children with ADHD and 18 aged-matched, typically developing children (TDC). ADHD subjects were divided into groups of only ADHD and ADHD + autism spectrum disorder (ASD). We employed the Continuous Performance Test (CPT) to measure attention. We focused on sleep spindle frequencies (12–14 Hz) in sleep stage 2 and performed a power spectral analysis using fast Fourier transform techniques and compared sleep spindles with the variability of reaction time in CPT. ResultsIn the CPT, reaction variabilities in ADHD and ADHD + ASD significantly differed from those in TDC. Twelve-hertz spindles were mainly distributed in the frontal pole and frontal area and 14-Hz spindles in the central area. The ratio of 12-Hz frontal spindle power was higher in ADHD than in TDC, especially in ADHD + ASD. Significant correlation between the ratio of 12-Hz spindles and reaction time variability was observed. ConclusionsTwelve-hertz frontal spindle EEG activity may have positive associations with sustained attention function. Slow frontal spindles may be useful as a biomarker of inattention in children with ADHD.

The sui generis Sydney Brenner

Sydney Brenner died on April 5, 2019, at age 92. His fame arose from three domains in which he operated with uncommon intellectual vibrancy. First were his prescient ideas and breakthrough experiments that defined the DNA genetic code and how the information it contains is transmitted into proteins. Second, in a later career, he developed a model organism, the roundworm Caenorhabditis elegans , to determine how the cells of an animal descend, one by one, along pathways of increasing specialization. Last was his beguiling skill as an intellectual sharpshooter, often surprising colleagues by the immediacy of his “take” of a problem, even ones somewhat beyond his ken. He always was very swift to the core point and instant with a wise reply. Sydney Brenner, 1927–2019. Image courtesy of Science Photo Library/James King-Holmes. Even though most of Brenner’s career was about the gene, it is to be emphasized that he was a keen biologist from the start. As an undergraduate at the University of Witwatersrand, South Africa’s top university, he strayed from his premedical curriculum and became adept at looking at various protozoa and culturing them in the laboratory. He also got keen about meiosis and wrote a brief report in Nature on the high frequency of multipolar spindles, a biological oddity he found in the sperm of the South African jumping shrew, Elephantulus (1). Captivated by chromosomes and genes at this early stage, he then read publications of Cyril Hinshelwood at Oxford, a chemist turned bacteriologist. Winning a scholarship to attend Oxford, it was with Hinshelwood that Brenner’s fascination with the gene was catalyzed into full action. There, he did important work on how phages can go into transient dormancy. It seems likely that in doing these experiments, he came to perceive that DNA can be active or silent, a … [↵][1]1Email: thoru.pederson{at}umassmed.edu. [1]: #xref-corresp-1-1

Interictal epileptiform discharges in sleep and the role of the thalamus in Encephalopathy related to Status Epilepticus during slow Sleep

EEG activation of interictal epileptiform discharges (IEDs) during NREM sleep is a well-described phenomenon that occurs in the majority of epileptic syndromes. In drug-resistant focal epilepsy, IED activation seems to be related to slow wave activity (SWA), especially during arousal fluctuations, namely phase A of the cyclic alternating pattern (CAP). Conversely, in childhood focal epileptic syndromes, including Encephalopathy related to Status Epilepticus during slow Sleep (ESES), IED activation seems primarily modulated by sleep-inducing and maintaining mechanisms as reflected by the dynamics of spindle frequency activity (SFA) rather than SWA. In this article, we will review the effect of sleep on IEDs with a particular attention on the activation and modulation of IEDs in ESES. Finally, we will discuss the role of the thalamus and cortico-thalamic circuitry in this syndrome.

Neurophysiological signature of gamma-hydroxybutyrate augmented sleep in male healthy volunteers may reflect biomimetic sleep enhancement: a randomized controlled trial.

Gamma-hydroxybutyrate (GHB) is an endogenous GHB/GABAB receptor agonist, which has demonstrated potency in consolidating sleep and reducing excessive daytime sleepiness in narcolepsy. Little is known whether GHB's efficacy reflects the promotion of physiological sleep mechanisms and no study has investigated its sleep consolidating effects under low sleep pressure. GHB (50 mg/kg p.o.) and placebo were administered in 20 young male volunteers at 2:30 a.m., the time when GHB is typically given in narcolepsy, in a randomized, double-blinded, crossover manner. Drug effects on sleep architecture and electroencephalographic (EEG) sleep spectra were analyzed. In addition, current source density (CSD) analysis was employed to identify the effects of GHB on the brain electrical sources of neuronal oscillations. Moreover, lagged-phase synchronization (LPS) analysis was applied to quantify the functional connectivity among sleep-relevant brain regions. GHB prolonged slow-wave sleep (stage N3) at the cost of rapid eye movement (REM) sleep. Furthermore, it enhanced delta-theta (0.5-8 Hz) activity in NREM and REM sleep, while reducing activity in the spindle frequency range (13-15 Hz) in sleep stage N2. The increase in delta power predominated in medial prefrontal cortex, parahippocampal and fusiform gyri, and posterior cingulate cortex. Theta power was particularly increased in the prefrontal cortex and both temporal poles. Moreover, the brain areas that showed increased theta power after GHB also exhibited increased lagged-phase synchronization among each other. Our study in healthy men revealed distinct similarities between GHB-augmented sleep and physiologically augmented sleep as seen in recovery sleep after prolonged wakefulness. The promotion of the sleep neurophysiological mechanisms by GHB may thus provide a rationale for GHB-induced sleep and waking quality in neuropsychiatric disorders beyond narcolepsy.

Non-REM Sleep Characteristics Predict Early Cognitive Impairment in an Aging Population.

Objective: Recent research suggests that sleep disorders or changes in sleep stages or EEG waveform precede over time the onset of the clinical signs of pathological cognitive impairment (e.g., Alzheimer's disease). The aim of this study was to identify biomarkers based on EEG power values and spindle characteristics during sleep that occur in the early stages of mild cognitive impairment (MCI) in older adults.Methods: This study was a case-control cross-sectional study with 1-year follow-up of cases. Patients with isolated subjective cognitive complaints (SCC) or MCI were recruited in the Bordeaux Memory Clinic (MEMENTO cohort). Cognitively normal controls were recruited. All participants were recorded with two successive polysomnography 1 year apart. Delta, theta, and sigma absolute spectral power and spindle characteristics (frequency, density, and amplitude) were analyzed from purified EEG during NREM and REM sleep periods during the entire second night.Results: Twenty-nine patients (8 males, age = 71 ± 7 years) and 29 controls were recruited at T0. Logistic regression analyses demonstrated that age-related cognitive impairment were associated with a reduced delta power (odds ratio (OR) 0.072, P < 0.05), theta power (OR 0.018, P < 0.01), sigma power (OR 0.033, P < 0.05), and spindle maximal amplitude (OR 0.002, P < 0.05) during NREM sleep. Variables were adjusted on age, gender, body mass index, educational level, and medication use. Seventeen patients were evaluated at 1-year follow-up. Correlations showed that changes in self-reported sleep complaints, sleep consolidation, and spindle characteristics (spectral power, maximal amplitude, duration, and frequency) were associated with cognitive impairment (P < 0.05).Conclusion: A reduction in slow-wave, theta and sigma activities, and a modification in spindle characteristics during NREM sleep are associated very early with a greater risk of the occurrence of cognitive impairment. Poor sleep consolidation, lower amplitude, and faster frequency of spindles may be early sleep biomarkers of worsening cognitive decline in older adults.

Intra-individual stability of NREM sleep quantitative EEG measures in obstructive sleep apnea.

Electroencephalography is collected routinely during clinical polysomnography, but is often utilised to simply determine sleep time to calculate apnea-hypopnea indices. Quantitative analysis of these data (quantitative electroencephalogram) may provide trait-like information to predict patient vulnerability to sleepiness. Measurements of trait-like characteristics need to have high test-retest reliability. We aimed to investigate the intra-individual stability of slow-wave (delta power) and spindle frequency (sigma power) activity during non-rapid eye movement sleep in patients with obstructive sleep apnea. We recorded sleep electroencephalograms during two overnight polysomnographic recordings in 61 patients with obstructive sleep apnea (median days between studies 47, inter-quartile range 53). Electroencephalograms recorded at C3-M2 derivation were quantitatively analysed using power spectral analysis following artefact removal. Relative delta (0.5-4.5 Hz) and sigma (12-15 Hz) power during non-rapid eye movement sleep were calculated. Intra-class correlation coefficients and Bland-Altman plots were used to assess agreement between nights. Intra-class correlation coefficients demonstrated good-to-excellent agreement in the delta and sigma frequencies between nights (intra-class correlation coefficients: 0.84, 0.89, respectively). Bland-Altman analysis of delta power showed a mean difference close to zero (-0.4, 95% limits of agreement -9.4, 8.7) and no heteroscedasticity with increasing power. Sigma power demonstrated heteroscedasticity, with reduced stability as sigma power increased. The mean difference of sigma power between nights was close to zero (0.1, 95% limits -1.6, 1.8). We have demonstrated the stability of slow-wave and spindle frequency electroencephalograms during non-rapid eye movement sleep within patients with obstructive sleep apnea. The electroencephalogram profile during non-rapid eye movement sleep may be a useful biomarker for predicting vulnerability to daytime impairment in obstructive sleep apnea and responsiveness to treatment.

CEP135 isoform dysregulation promotes centrosome amplification in breast cancer cells.

The centrosome, composed of two centrioles surrounded by pericentriolar material, is the cell’s central microtubule-organizing center. Centrosome duplication is coupled with the cell cycle such that centrosomes duplicate once in S phase. Loss of such coupling produces supernumerary centrosomes, a condition called centrosome amplification (CA). CA promotes cell invasion and chromosome instability, two hallmarks of cancer. We examined the contribution of centriole overduplication to CA and the consequences for genomic stability in breast cancer cells. CEP135, a centriole assembly protein, is dysregulated in some breast cancers. We previously identified a short isoform of CEP135, CEP135mini, that represses centriole duplication. Here, we show that the relative level of full-length CEP135 (CEP135full) to CEP135mini (the CEP135full:mini ratio) is increased in breast cancer cell lines with high CA. Inducing expression of CEP135full in breast cancer cells increases the frequency of CA, multipolar spindles, anaphase-lagging chromosomes, and micronuclei. Conversely, inducing expression of CEP135mini reduces centrosome number. The differential expression of the CEP135 isoforms in vivo is generated by alternative polyadenylation. Directed genetic mutations near the CEP135mini alternative polyadenylation signal reduces the CEP135full:mini ratio and decreases CA. We conclude that dysregulation of CEP135 isoforms promotes centriole overduplication and contributes to chromosome segregation errors in breast cancer cells.

Trait-like characteristics of sleep EEG power spectra in adolescents across sleep opportunity manipulations.

The electroencephalographic power spectra of non‐rapid eye movement sleep in adults demonstrate trait‐like consistency within participants across multiple nights, even when prior sleep deprivation is present. Here, we examined the extent to which this finding applies to adolescents who are habitually sleep restricted on school‐days and sleep longer on weekends. We evaluated 78 adolescents across three sleep restriction groups who underwent different permutations of adequate sleep (9 hr time‐in‐bed), sleep restriction (5 hr time‐in‐bed), afternoon naps (1 hr afternoon) and recovery sleep (9 hr time‐in‐bed) that simulate behaviour on school‐days and weekends. The control group comprised a further 22 adolescents who had 9 hr of sleep opportunity each night. Intra‐class correlation coefficients showed moderate to almost perfect within‐subject stability in electroencephalographic power spectra across multiple nights in both sleep restriction and control groups, even when changes to sleep macrostructure were observed. While nocturnal intra‐class correlation metrics were lower in the low‐frequency and spindle frequency bins in the sleep restriction compared with the control group, hierarchical clustering measures could still identify multi‐night electroencephalographic spectra as originating from the same individual. The trait‐like characteristics of electroencephalographic spectra from an adolescent remain identifiable despite the disruptive effects of multi‐night sleep restriction to sleep architecture.

Daytime Central Thalamic Deep Brain Stimulation Modulates Sleep Dynamics in the Severely Injured Brain: Mechanistic Insights and a Novel Framework for Alpha-Delta Sleep Generation.

Loss of organized sleep electrophysiology is a characteristic finding following severe brain injury. The return of structured elements of sleep architecture has been associated with positive prognosis across injury etiologies, suggesting a role for sleep dynamics as biomarkers of wakeful neuronal circuit function. In a continuing study of one minimally conscious state patient studied over the course of ~8½ years, we sought to investigate whether changes in daytime brain activation induced by central thalamic deep brain stimulation (CT-DBS) influenced sleep electrophysiology. In this patient subject, we previously reported significant improvements in sleep electrophysiology during 5½ years of CT-DBS treatment, including increased sleep spindle frequency and SWS delta power. We now present novel findings that many of these improvements in sleep electrophysiology regress following CT-DBS discontinuation; these regressions in sleep features correlate with a significant decrease in behavioral responsiveness. We also observe the re-emergence of alpha-delta sleep, which had been previously suppressed by daytime CT-DBS in this patient subject. Importantly, CT-DBS was only active during the daytime and has been proposed to mediate recovery of consciousness by driving synaptic activity across frontostriatal systems through the enhancement of thalamocortical output. Accordingly, the improvement of sleep dynamics during daytime CT-DBS and their subsequent regression following CT-DBS discontinuation implicates wakeful synaptic activity as a robust modulator of sleep electrophysiology. We interpret these findings in the context of the “synaptic homeostasis hypothesis,” whereby we propose that daytime upregulation of thalamocortical output in the severely injured brain may facilitate organized frontocortical circuit activation and yield net synaptic potentiation during wakefulness, providing a homeostatic drive that reconstitutes sleep dynamics over time. Furthermore, we consider common large-scale network dynamics across several neuropsychiatric disorders in which alpha-delta sleep has been documented, allowing us to formulate a novel mechanistic framework for alpha-delta sleep generation. We conclude that the bi-directional modulation of sleep electrophysiology by daytime thalamocortical activity in the severely injured brain: (1) emphasizes the cyclical carry-over effects of state-dependent circuit activation on large-scale brain dynamics, and (2) further implicates sleep electrophysiology as a sensitive indicator of wakeful brain activation and covert functional recovery in the severely injured brain.

Slow spindles are associated with cortical high frequency activity

Thalamocortical network shows self-sustained oscillations in a broad frequency range especially during slow wave sleep when cortical neurons show synchronized transitions between a quiescent down state and an active up state with beta and gamma oscillations. Inconsistent with previous models, thalamocortical spindles are separated into slow spindles (8_12 Hz) and fast spindles (13_17 Hz) with differential properties. We proposed that cortical high frequency (∼ 25 Hz) activity during up states is the key ingredient for the generation of slow spindles. In fact, the nonlinear interaction between cortical high frequency and thalamic oscillations at fast spindle frequency reproduces oscillations in the range of the difference between the two frequencies that lies into the range of slow spindle. The developed simple deterministic thalamocortical model is able to reproduce up and down states with stochastic high-frequency up-state activity as well as both fast and slow spindles. In agreement with the previous experimental observations, the fast and slow spindles are generated at opposing phases of the up state. To further confirm the causal relationship between slow spindles and cortical high frequency oscillations, we next showed that externally applied high frequency stimulation enhanced the slow spindle activity. Moreover, the prediction of the model was validated experimentally by recording EEG from subjects during nap. Both model and experimental results show increase in high frequency activity before slow spindles. Our findings suggest the important role of cortical high frequency activity in the generation of slow spindles.

Higher sleep spindle activity is associated with fewer false memories in adolescent girls.

Sleep facilitates the extraction of semantic regularities amongst newly encoded memories, which may also lead to increased false memories. We investigated sleep stage proportions and sleep spindles in the recollection of adolescents' false memories, and their potential sex-specific differences. 196 adolescents (mean age 16.9 y; SD = 0.1, 61% girls) underwent the Deese, Roediger & McDermott (DRM) false memory procedure and overnight polysomnography, with free recall the following morning. Sleep was scored manually into stages 1, 2, 3 and REM. Stage 2 sleep spindle frequency, density, and peak amplitude were used as measures of spindle activity for slow (10-13 Hz) and fast (13-16 Hz) ranges. In girls, a lower number of critical lures was associated with higher spindle frequency (p ≤ 0.01), density (p ≤ 0.01), and amplitude (p = 0.03). Additionally, girls' longer sleep duration was associated with more intrusion words (p = 0.03), but not with critical lures. These associations survived adjustment for age, pubertal status, and intelligence. No significant results emerged in boys. In adolescent girls, higher spindle activity was associated with fewer critical lures being falsely recalled in the DRM paradigm. Unlike studies using adult participants, we did not observe any association between slow-wave sleep and false memory recollection.

Sleep spindles are altered in early- but not late-onset nightmare recallers

Nightmares are a common sleep disorder, defined as highly disturbing mentation which usually awakens the individual from rapid eye movement (REM) sleep. While nightmares are mainly a REM sleep phenomenon, Picard-Deland et al., (2017) recently showed an association between nightmare recall and sleep spindles, which are a non-rapid eye movement (NREM) oscillatory feature. Their results pointed to fewer slow spindles and a higher oscillatory frequency for fast spindles among frequent nightmare recallers compared with controls. To test the suggestion that nightmares stem from changes to emotional neural circuits arising in early childhood (Nielsen, 2017), including early changes in sleep spindles (Scholle et al., 2007), we investigated if the spindle features of early-onset nightmare recallers (ie, recalling nightmares since childhood) (N = 22), differed from those of late-onset nightmare recallers (ie, since adolescence or adulthood) (N = 11), or from those of controls (N = 23). A retrospective analysis of the sleep spindles of 56 participants who had undergone a polysomnographically-recorded morning nap revealed that Early starters uniquely exhibited lower slow spindle densities in five of six derivations (all p < 0.045) and higher fast spindle frequencies in all six derivations (all p < 0.015). These results add precision to previously reported findings for Nightmare recallers: spindle differences are shown to hold only for Early starters. The lifelong occurrence of nightmares may be closely tied to disruptions in the normal development of spindle generation processes occurring early in development.

Spindle activity in young children with autism, developmental delay, or typical development.

To determine whether spindle activity differs in young children with and without autism. We investigated differences in spindle density, duration, and oscillatory features in 135 young children with autism, developmental delay without autism (DD), or typical development (TD) and secondarily assessed the dimensional relationship between spindle density and both cognitive ability and social functioning. Compared to TD, both spindle density (Cohen d 0.93, 95% confidence interval [CI] 0.49-1.37) and duration (Cohen d 0.58, 95% CI 0.15-1.01) were significantly decreased in autism. Spindle density was also significantly reduced in autism compared to DD (Cohen d 0.61, 95% CI 0.13-1.09). Decreased spindle frequency in autism compared to both TD (Cohen d 0.47, 95% CI 0.04-0.90) and DD (Cohen d 0.58, 95% CI 0.10-1.06) did not survive correction. The DD group did not differ significantly from the TD group on any spindle parameter. These results, suggesting a relationship between spindle density and autism but not DD, were further illustrated in exploratory analyses, wherein nonverbal ratio IQ (RIQ) and the Vineland Socialization domain standard score were strongly correlated with spindle density in the full sample (r = 0.33, p ≤ 001 and r = 0.41, p ≤ 001, respectively) but not within group. After nonverbal RIQ was accounted for, the relationship between spindle density and Vineland Socialization remained statistically significant (r = 0.23, p < 0.01). However, Vineland Socialization scores accounted for the relationship between spindle density and nonverbal RIQ (r = 0.04, p = 0.67). In a large cohort of young children with autism, spindle density was reduced compared to groups of age-matched children with DD or TD. Alterations in the maturational trajectory of spindles may provide valuable insight into the neurophysiologic differences related to behavior in disorders of neurodevelopment.

Protein kinase C zeta suppresses low- or high-grade colorectal cancer (CRC) phenotypes by interphase centrosome anchoring.

Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring. PKCz regulates interdependent processes that control centrosome positioning. Among these, interaction between the cytoskeletal linker protein ezrin and its binding partner NHERF1 promotes the formation of a localized cue for anchoring interphase centrosomes to the cell cortex. Perturbation of these phenomena induced different outcomes in cells with single or extra centrosomes. Defective anchoring of a single centrosome promoted bipolar spindle misorientation, multi‐lumen formation, and aberrant epithelial stratification. Collectively, these disturbances induce cribriform multicellular morphology that is typical of some categories of low‐grade CRC. By contrast, defective anchoring of extra centrosomes promoted multipolar spindle formation, chromosomal instability (CIN), disruption of glandular morphology, and cell outgrowth across the extracellular matrix interface characteristic of aggressive, high‐grade CRC. Because PKCz enhances apical NHERF1 intensity in 3D epithelial cultures, we used an immunohistochemical (IHC) assay of apical NHERF1 intensity as an indirect readout of PKCz activity in translational studies. We show that apical NHERF1 IHC intensity is inversely associated with multipolar spindle frequency and high‐grade morphology in formalin‐fixed human CRC samples. To conclude, defective PKCz control of interphase centrosome anchoring may underlie distinct categories of mitotic slippage that shape the development of low‐ or high‐grade CRC phenotypes. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.