Rhythmic Oscillations Research Articles

Fresh insights into the light‐induced pineal gland circadian rhythm transmission mechanism derived from mRNA and miRNA profiling

AbstractThe circadian clock significantly impacts animal health and productivity, with light playing a crucial role in regulating circadian rhythms. However, the mechanisms behind light‐induced circadian transmission remain unclear, particularly in light‐sensitive avian species. The pineal gland is a key component acting as the photosensitive master oscillator in the avian clock system. Using transcriptome sequencing and small RNA sequencing technologies, we identified circadian genes and miRNAs in the chick pineal gland under light–dark and sudden constant‐light conditions. We observed rhythmic oscillations in up to 1299 genes during the light–dark cycle, with 400 genes maintaining rhythms under constant light. Our findings highlight the light‐sensitive temporal organization in birds as the phase distribution of circadian genes in the pineal gland correlates with light exposure changes. A novel regulatory mechanism involving light, cyclic adenosine monophosphate, cyclic guanosine monophosphate, light‐sensitive miRNAs, such as gga‐miR‐34b‐5p, and light‐sensitive circadian genes, such as CRY2, was discovered to participate in the light input system of the chick pineal clock, through which light regulates the oscillators and outputs of the circadian clock system. Additionally, transcriptomic analysis, liquid chromatography–mass spectrometry, and Oil Red O staining revealed cyclic changes in lipid synthesis and metabolism throughout the circadian day, which may be a key mechanism through which the circadian clock influences pineal physiology. Our results enhance the understanding of light‐induced circadian transmission mechanisms and identify potential targets for optimizing the circadian clock through light.

Integrating brainstem and cortical functional architectures.

The brainstem is a fundamental component of the central nervous system, yet it is typically excluded from in vivo human brain mapping efforts, precluding a complete understanding of how the brainstem influences cortical function. In this study, we used high-resolution 7-Tesla functional magnetic resonance imaging to derive a functional connectome encompassing cortex and 58 brainstem nuclei spanning the midbrain, pons and medulla. We identified a compact set of integrative hubs in the brainstem with widespread connectivity with cerebral cortex. Patterns of connectivity between brainstem and cerebral cortex manifest as neurophysiological oscillatory rhythms, patterns of cognitive functional specialization and the unimodal-transmodal functional hierarchy. This persistent alignment between cortical functional topographies and brainstem nuclei is shaped by the spatial arrangement of multiple neurotransmitter receptors and transporters. We replicated all findings using 3-Tesla data from the same participants. Collectively, this work demonstrates that multiple organizational features of cortical activity can be traced back to the brainstem.

7170 Plasticity of the Hypothalamic Tuberoinfundibular Dopaminergic Neuronal Network in Lactating Rats

Abstract Disclosure: P. Papaioannou: None. T. Georgescu: None. D.R. Grattan: None. S. Bunn: None. S. Yip: None. The tuberoinfundibular dopaminergic (TIDA) neurons play a crucial role in regulating prolactin secretion. Their synchronized network activity with slow but highly rhythmic firing pattern is important for dopamine release in rats[1]. While this unique TIDA network activity is vital for prolactin negative feedback in non-lactating conditions, its behaviour during lactation, when prolactin demand is high, remains unknown. Our hypothesis posited that the TIDA neuronal network in lactating rats becomes desynchronized, disrupting the negative feedback loop. To test this, we utilized ex-vivo Ca2+ imaging to simultaneously monitor population-wide TIDA neuron activity in non-lactating (NL; n=13) and lactating (L; n=10) rats injected with a cre-inducible adeno-associated virus (AAV) containing the Ca2+ indicator, GCaMP6s, into their arcuate nucleus. Analysis of neuronal network synchronicity revealed significant desynchronization in the TIDA network during lactation, as indicated by a markedly lower mean correlation coefficient matrix (CM) compared to non-lactating conditions (NL: 0.87±0.02, n= 26 sections vs L: 0.22±0.03, n=29 sections; p<0.001, Student’s t-test). Furthermore, the oscillatory activity patterns of these desynchronized TIDA neurons displayed a significantly lower cell rhythmicity index (RI) in lactating animals compared to non-lactating ones (NL: 0.17±0.01, n=186 cells vs L: 0.70±0.02, n=77 cells; p<0.001, Student’s t-test). Interestingly, within these low rhythmic neurons, some exhibited higher while others showed lower firing frequencies compared to non-lactating TIDA neurons. After 7 days post-weaning (n=4 animals), the TIDA network activity returned to non-lactating behaviour (CM = 0.85 ± 0.04, n=6 sections and RI = 0.17±0.01; n=47 cells). In summary, our findings demonstrate a reversible reconfiguration of the TIDA neuronal networks during lactation, characterized by low rhythmic oscillations and individual unique firing patterns, leading to diminished intercellular synchrony that may impede dopamine release, ultimately facilitating prolactin release to support lactation. Once weaned, the TIDA neuronal network reset to NL state to allow a new reproductive cycle. [1] Lyons, D. J., Horjales-Araujo, E. & Broberger, C. Synchronized network oscillations in rat tuberoinfundibular dopamine neurons: switch to tonic discharge by thyrotropin-releasing hormone. Neuron 65, 217-229, doi:10.1016/j.neuron.2009.12.024 (2010). Presentation: 6/2/2024

Characterizing the rhythmic oscillations of gut bacterial and fungal communities and their rhythmic interactions in male cynomolgus monkeys.

The rhythmic oscillation of gut microbiota can impact the physiology activity and disease susceptibility of the host. Until now, most of the studies are focused on bacterial microbes, ignoring other components of gut microbes, such as fungal microbes (mycobiota). Besides, only few studies have addressed the rhythmic correlations between gut bacteria and fungi. Here, we analyzed the rhythmic oscillations of bacterial and fungal communities in male cynomolgus monkeys by performing 16S rRNA and ITS amplicon sequencing. Apart from identifying the rhythmically oscillated bacterial and fungal microbes, we conducted the correlation analysis between these two microbial communities and found that the intestinal bacteria and fungi exhibited close interactions rhythmically, with the most interactions occurring at ZT12. Thus, our study not only investigated the rhythmic oscillations of gut bacterial and fungal communities in male cynomolgus monkeys but also uncovered their rhythmic interactions.

The gamma-band activity model of the near-death experience: a critique and a reinterpretation.

Near-death experience (NDE) is a transcendent mental event of uncertain etiology that arises on the cusp of biological death. Since the discovery of NDE in the mid-1970s, multiple neuroscientific theories have been developed in an attempt to account for it in strictly materialistic or reductionistic terms. Therefore, in this conception, NDE is at most an extraordinary hallucination without any otherworldly, spiritual, or supernatural denotations. During the last decade or so, a number of animal and clinical studies have emerged which reported that about the time of death, there may be a surge of high frequency electroencephalogram (EEG) at a time when cortical electrical activity is otherwise at a very low ebb. This oscillatory rhythm falls within the range of the enigmatic brain wave-labelled gamma-band activity (GBA). Therefore, it has been proposed that this brief, paradoxical, and perimortem burst of the GBA may represent the neural foundation of the NDE. This study examines three separate but related questions concerning this phenomenon. The first problem pertains to the electrogenesis of standard GBA and the extent to which authentic cerebral activity has been contaminated by myogenic artifacts. The second problem involves the question of whether agents that can mimic NDE are also underlain by GBA. The third question concerns the electrogenesis of the surge in GBA itself. It has been contended that this is neither cortical nor myogenic in origin. Rather, it arises in a subcortical (amygdaloid) location but is recorded at the cortex via volume conduction, thereby mimicking standard GBA. Although this surge of GBA contains genuine electrophysiological activity and is an intriguing and provocative finding, there is little evidence to suggest that it could act as a kind of neurobiological skeleton for a phenomenon such as NDE.

Novel insights into the circadian modulation of lipid metabolism in chicken livers revealed by RNA sequencing and weighted gene co-expression network analysis

The circadian clock is crucial for maintaining lipid metabolism homeostasis in mammals. Despite the economic importance of fat content in poultry, research on the regulatory effects and molecular mechanisms of the circadian clock on avian hepatic lipid metabolism has been limited. In this study, we observed significant diurnal variations (P<0.05) in triglyceride (TG), free fatty acids (FFA), fatty acid synthase (FAS), and total cholesterol (TC) levels in the chicken embryonic liver under 12-h light/12-h dark incubation conditions, with TG, FFA, and TC concentrations showing significant cosine rhythmic oscillations (P<0.05). However, such rhythmic variations were not observed under complete darkness incubation conditions. Using transcriptome sequencing technology, we identified 157 genes significantly upregulated at night and 313 genes significantly upregulated during the 12-h light/12-h dark cycle. These circadian differential genes are involved in processes and pathways such as lipid catabolic process regulation, meiotic cell cycle, circadian rhythm regulation, positive regulation of the MAPK cascade, and glycerolipid metabolism. Weighted gene co-expression network analysis (WGCNA) revealed 3 modules-green, blue, and red-that significantly correlate with FFA, FAS, and TG, respectively. Genes within these modules were enriched in processes and pathways including the cell cycle, light stimulus response, circadian rhythm regulation, phosphorylation, positive regulation of the MAPK cascade, and lipid biosynthesis. Notably, we identified ten hub genes, including protein kinase C delta (PRKCD), polo like kinase 4 (PLK4), clock circadian regulator (CLOCK), steroid 5 alpha-reductase 3 (SRD5A3), BUB1 mitotic checkpoint serine/threonine kinase (BUB1B), shugoshin 1 (SGO1), NDC80 kinetochore complex component (NDC80), NIMA related kinase 2 (NEK2), minichromosome maintenance complex component 4 (MCM4), polo like kinase 1 (PLK1), potentially link circadian regulation with lipid metabolic homeostasis. These findings demonstrate the regulatory role of the circadian clock in chicken liver lipid metabolism homeostasis and provide a theoretical basis and molecular targets for optimizing the circadian clock to reduce excessive fat deposition in chickens, which is significant for the healthy development of the poultry industry.

Molecular characterization of PSEUDO RESPONSE REGULATOR family in Rosaceae and function of PbPRR59a and PbPRR59b in flowering regulation

BackgroundPSEUDO RESPONSE REGULATOR (PRR) genes are essential components of circadian clock, playing vital roles in multiple processes including plant growth, flowering and stress response. Nonetheless, little is known about the evolution and function of PRR family in Rosaceae species.ResultsIn this study, a total of 43 PRR genes in seven Rosaceae species were identified through comprehensive analysis. The evolutionary relationships were analyzed with phylogenetic tree, duplication events and synteny. PRR genes were classified into three groups (PRR1, PRR5/9, PRR3/7). The expansion of PRR family was mainly derived from dispersed and whole-genome duplication events. Purifying selection was the major force for PRR family evolution. Synteny analysis indicated the existence of multiple orthologous PRR gene pairs between pear and other Rosaceae species. Moreover, the conserved motifs of eight PbPRR proteins supported the phylogenetic relationship. PRR genes showed diverse expression pattern in various tissues of pear (Pyrus bretschneideri). Transcript analysis under 12-h light/ dark cycle and constant light conditions revealed that PRR genes exhibited distinct rhythmic oscillations in pear. PbPRR59a and PbPRR59b highly homologous to AtPRR5 and AtPRR9 were cloned for further functional verification. PbPRR59a and PbPRR59b proteins were localized in the nucleus. The ectopic overexpression of PbPRR59a and PbPRR59b significantly delayed flowering in Arabidopsis transgenic plants by repress the expression of AtGI, AtCO and AtFT under long-day conditions.ConclusionsThese results provide information for exploring the evolution of PRR genes in plants, and contribute to the subsequent functional studies of PRR genes in pear and other Rosaceae species.

The eukaryotic translation initiation factor eIF4E regulates flowering and circadian rhythm in Arabidopsis.

Translation initiation is a critical, rate-limiting step in protein synthesis. The eukaryotic translation initiation factor 4E (eIF4E) plays an essential role in this process. However, the mechanisms by which eIF4E-dependent translation initiation regulates plant growth and development remain not fully understood. In this study, we found that Arabidopsis eIF4E proteins are distributed in both the nucleus and cytoplasm, with only the cytoplasmic eIF4E being involved in the control of photoperiodic flowering. Genome-wide translation profiling using Ribo-tag sequencing reveals that eIF4E may regulate plant flowering by maintaining the homeostatic translation of components in the photoperiodic flowering pathway. eIF4E not only regulates the translation of flowering genes such as FLOWERING LOCUS T (FT) and FLOWERING LOCUS D (FLD) but also influences the translation of circadian genes like CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and PSEUDO-RESPONSE REGULATOR 9 (PRR9). Consistently, our results show that the eIF4E modulates the rhythmic oscillation of the circadian clock. Together, our study provides mechanistic insights into how the protein translation regulates multiple developmental processes in Arabidopsis, including the circadian clock and photoperiodic flowering.

CuO nanoparticles' effect on the photosynthetic performance in seed tissues of Inga laurina (Fabaceae).

Copper oxide nanoparticles (CuONPs) have been produced on a large scale because they can be applied across various fields, especially in nano-enabled healthcare and agricultural products. However, the increasing use of CuONPs leads to their release and accumulation into the environment. The CuONPs uptaken by seeds and their implications on germination behavior have been reported, but little is known or understood about their impact on photosynthesis in seed tissues. To fill knowledge gaps, this study evaluated the effects of CuONP concentrations (0-300mg L-1) on the photosynthetic activity of Inga laurina seeds. The microscopy data showed that CuONPs had an average size distribution of 57.5 ± 0.7nm. Copper ion release and production of reactive oxygen species (ROS) by CuONPs were also evaluated by dialysis and spectroscopy experiments, respectively. CuONPs were not able to intrinsically generate ROS and released a low content of Cu2⁺ ions (4.5%, w/w). Time evolution of chlorophyll fluorescence imaging and laser-induced fluorescence spectroscopy were used to monitor the seeds subjected to nanoparticles during 168h. The data demonstrate that CuONPs affected the steady-state maximum chlorophyll fluorescence ( ), the photochemical efficiency of photosystem II ( ), and non-photochemical quenching ( ) of Inga laurina seeds over time. Besides, the significantly increased at the seed development stage, near the root protrusion stage, probably due to energy dissipation at this germination step. Additionally, the results indicated that CuONPs can change the oscillatory rhythms of energy dissipation of the seeds, disturbing the circadian clock. In conclusion, the results indicate that CuONPs can affect the photosynthetic behavior of I. laurina seeds. These findings open opportunities for using chlorophyll fluorescence as a non-destructive tool to evaluate nanoparticle impact on photosynthetic activity in seed tissues.

Efferent pathways from the suprachiasmatic nucleus to the horizontal limbs of diagonal band promote NREM sleep during the dark phase in mice

The regulation of circadian rhythms and the sleep–wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep–wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN–HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non–rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN–HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep–wake states regulation.

Autonomous Oscillatory Mitochondrial Respiratory Activity: Results of a Systematic Analysis Show Heterogeneity in Different In Vitro-Synchronized Cancer Cells.

Circadian oscillations of several physiological and behavioral processes are an established process in all the organisms anticipating the geophysical changes recurring during the day. The time-keeping mechanism is controlled by a transcription translation feedback loop involving a set of well-characterized transcription factors. The synchronization of cells, controlled at the organismal level by a brain central clock, can be mimicked in vitro, pointing to the notion that all the cells are endowed with an autonomous time-keeping system. Metabolism undergoes circadian control, including the mitochondrial terminal catabolic pathways, culminating under aerobic conditions in the electron transfer to oxygen through the respiratory chain coupled to the ATP synthesis according to the oxidative phosphorylation chemiosmotic mechanism. In this study, we expanded upon previous isolated observations by utilizing multiple cell types, employing various synchronization protocols and different methodologies to measure mitochondrial oxygen consumption rates under conditions simulating various metabolic stressors. The results obtained clearly demonstrate that mitochondrial respiratory activity undergoes rhythmic oscillations in all tested cell types, regardless of their individual respiratory proficiency, indicating a phenomenon that can be generalized. However, notably, while primary cell types exhibited similar rhythmic respiratory profiles, cancer-derived cell lines displayed highly heterogeneous rhythmic changes. This observation confirms on the one hand the dysregulation of the circadian control of the oxidative metabolism observed in cancer, likely contributing to its development, and on the other hand underscores the necessity of personalized chronotherapy, which necessitates a detailed characterization of the cancer chronotype.

Life in Lab: Chemically Fueled Systems Chemistry for Emergent Properties

Understanding the emergence of complex properties in dissipative non‐equilibrium systems is crucial for unraveling the mysteries of life processes. The review focuses on the documented research on chemically fueled autonomous systems, self‐sorting towards compartmentalization, self‐replication via autocatalysis, and rhythmic chemical oscillators. In addition to that, the review also discusses newly introduced reactions and dynamic combinatorial libraries in dissipative systems.

Forkhead box protein FOXK1 disrupts the circadian rhythm to promote breast tumorigenesis in response to insulin resistance

The dysregulation of circadian rhythm oscillation is a prominent feature of various solid tumors. Thus, clarifying the molecular mechanisms that maintain the circadian clock is important. In the present study, we revealed that the transcription factor forkhead box FOXK1 functions as an oncogene in breast cancer. We showed that FOXK1 recruits multiple transcription corepressor complexes, including NCoR/SMRT, SIN3A, NuRD, and REST/CoREST. Among them, the FOXK1/NCoR/SIN3A complex transcriptionally regulates a cohort of genes, including CLOCK, PER2, and CRY2, that are critically involved in the circadian rhythm. The complex promoted the proliferation of breast cancer cells by disturbing the circadian rhythm oscillation. Notably, the nuclear expression of FOXK1 was positively correlated with tumor grade. Insulin resistance gradually became more severe with tumor progression and was accompanied by the increased expression of OGT, which caused the nuclear translocation and increased expression of FOXK1. Additionally, we found that metformin downregulates FOXK1 and exports it from the nucleus, while HDAC inhibitors (HDACi) inhibit the FOXK1-related enzymatic activity. Combined treatment enhanced the expression of circadian clock genes through the regulation of FOXK1, thereby exerting an antitumor effect, indicating that highly nuclear FOXK1-expressing breast cancers are potential candidates for the combined application of metformin and HDACi.

Possible mechanisms to improve sleep spindles via closed loop stimulation during slow wave sleep: A computational study.

Sleep spindles are one of the prominent EEG oscillatory rhythms of non-rapid eye movement sleep. In the memory consolidation, these oscillations have an important role in the processes of long-term potentiation and synaptic plasticity. Moreover, the activity (spindle density and/or sigma power) of spindles has a linear association with learning performance in different paradigms. According to the experimental observations, the sleep spindle activity can be improved by closed loop acoustic stimulations (CLAS) which eventually improve memory performance. To examine the effects of CLAS on spindles, we propose a biophysical thalamocortical model for slow oscillations (SOs) and sleep spindles. In addition, closed loop stimulation protocols are applied on a thalamic network. Our model results show that the power of spindles is increased when stimulation cues are applied at the commencing of an SO Down-to-Up-state transition, but that activity gradually decreases when cues are applied with an increased time delay from this SO phase. Conversely, stimulation is not effective when cues are applied during the transition of an Up-to-Down-state. Furthermore, our model suggests that a strong inhibitory input from the reticular (RE) layer to the thalamocortical (TC) layer in the thalamic network shifts leads to an emergence of spindle activity at the Up-to-Down-state transition (rather than at Down-to-Up-state transition), and the spindle frequency is also reduced (8-11 Hz) by thalamic inhibition.

Leg stereotypy syndrome: phenomenological and quantitative analysis.

Leg stereotypy syndrome (LSS) is a very common, yet underrecognized condition. The pathophysiology of the condition is not well understood. To evaluate and describe the visual kinematic characteristics of the repetitive leg movements in individuals with LSS. In this study, we identified and videotaped individuals diagnosed with LSS at the Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas between 2000 and 2023. Only patients with LSS and without any co-morbidities were included in the study. Their medical records were carefully reviewed, and the demographic and clinical data were entered into a database. Video recordings of the repetitive leg movements were then analyzed using TremAn software. We identified 14 individuals with LSS who were videotaped at our center. The videos of the 5 cases were too brief and therefore not suitable for TremAn quantitative analysis. The remaining 9 individuals exhibited regular rhythmic oscillations of the legs. Among these, two individuals displayed rhythmic movements only in video segments where their legs were in crossed positions. The other 7 individuals had regular rhythmic oscillations, always with the toes resting on the floor with the heels raised. Frequency analysis showed values between 4.5 and 6.5Hz, fairly consistent with a variance below 0.5Hz in individual cases. The oscillation frequency changed from 5.7 Hz to 2.7 Hz while standing. In this study, 6 of 9 individuals with LSS showed 4.5-6.5Hz regular rhythmic leg movements. Studies involving a larger LSS population with additional electrophysiological evaluations are needed to obtain further insights into this common movement disorder.

The dynamics of cyclic‐periodic phenomena during non‐rapid and rapid eye movement sleep

SummarySleep is a complex physiological state characterized by distinct stages, each exhibiting unique electroencephalographic patterns and physiological phenomena. Sleep research has unveiled the presence of intricate cyclic‐periodic phenomena during both non‐rapid eye movement and rapid eye movement sleep stages. These phenomena encompass a spectrum of rhythmic oscillations and periodic events, including cyclic alternating pattern, periodic leg movements during sleep, respiratory‐related events such as apneas, and heart rate variability. This narrative review synthesizes empirical findings and theoretical frameworks to elucidate the dynamics, interplay and implications of cyclic‐periodic phenomena within the context of sleep physiology. Furthermore, it invokes the clinical relevance of these phenomena in the diagnosis and management of sleep disorders.

Identification of novel pharmacological activators of circadian clock with anti-adipogenic properties

The circadian clock drives rhythmic oscillations of metabolic processes to orchestrate metabolic homeostasis, and disruption of this mechanism predisposes to obesity and insulin resistance. Preserving or augmenting clock function could be a potential therapeutic target for metabolic diseases, particularly with the wide-spread of circadian misalignment in a modern lifestyle. To date, targeting the clock for metabolic disease prevention or treatment remains to be explored. Adipocyte possesses cell-autonomous clocks that exert transcriptional control of the Wnt pathway to inhibit adipocyte development. Using a high through-put screening pipeline, we recently identified Chlorhexidine as a novel clock-activating molecule that targets the key driver of the circadian clock transcriptional feedback loop, the CLOCK protein. Based on clock function in suppressing adipogenesis, we hypothesize that Chlorhexidine and related compounds may possess adipogenic-inhibitory properties suitable for anti-obesity drug development. In distinct adipogenic progenitor models, we demonstrate the activity of Chlorhexidine in inhibiting adipogenic lineage commitment and terminal differentiation. Furthermore, we report the structural optimization of Chlorhexidine chemical scaffold that led to the discovery of new analogs with improved anti-adipogenic effcacy. Consistent with its activity for clock activation, in adipogenic progenitors containing a Period2::dLuc luciferase reporter, Chlorhexidine induced significant shortening of clock period length with induction of core clock components. Chlorhexidine treatment of adipogenic mesenchymal precursors robustly suppressed their adipogenic maturation, with a comparable effect observed on inhibiting terminal differentiation of primary preadipocytes in a clock-dependent manner. Mechanistically, Chlorhexidine stimulates clock-controlled Wnt signaling that mediates its anti-adipogenic effect. Through medicinal chemistry modification of its chemical scaffold, we generated a panel of Chlorhexidine analogs with validation for their clock-modulatory activities. Structure activity relationship analysis of these analogs led to the identification of CM002 as a new clock activator with improved clock-dependent anti-adipogenic activity. Collectively, our findings uncovered a new class of clock-modulatory compounds that inhibit adipocyte development for potential anti-obesity drug discovery and provide clock-targeting chemical probes for dissecting clock function in metabolic physiology. This project was supported by grants from National Institute of Aging R56AG080294 and Arthur Riggs-Diabetes &amp; Metabolism Research Institute T2D and T1D Innovative Awards to KM. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Parent-child coregulation as a dynamic system: a commentary on Wass etal. (2024).

In this commentary, I argue that including and operationalizing allostatic processes will become increasingly important in future research on parent-child biobehavioral coregulation. In particular, the conceptualization and modeling of dyadic oscillatory rhythms that align in expected ways with the child's developmental stage and that distinguish typical and atypical development will be useful in future work. Despite the inherent asymmetry characteristic of parent-child relationships, we should not forget to consider the child's effects on the parent within and across time, the additional environmental demands upon parents that shape parent-child coregulation, and variations in parent-child asymmetry by parental risk factors. Studying risk factors that are dyadic in nature, such as child maltreatment, may be particularly informative in gaining a deeper understanding of how parent-child coregulation interfaces with developmental psychopathology. To best model parent-child coregulation as a dynamic system, it will be critical to employ more nonlinear analytic models and better represent the multiple hierarchical domains of coregulation and their interactions, including affect, cognition, behavior, and biology. Finally, in future research, a deeper application of existing dyadic and dynamic theories, as well as the generation of new dyadic developmental theories, will aid us in obtaining a stronger understanding of the developmental function and intervention implications of parent-child biobehavioral coregulation.

Analysis of hippocampal local field potentials by diffusion mapped delay coordinates

Spatial navigation through novel spaces and to known goal locations recruits multiple integrated structures in the mammalian brain. Within this extended network, the hippocampus enables formation and retrieval of cognitive spatial maps and contributes to decision making at choice points. Exploration and navigation to known goal locations produce synchronous activity of hippocampal neurons resulting in rhythmic oscillation events in local networks. Power of specific oscillatory frequencies and numbers of these events recorded in local field potentials correlate with distinct cognitive aspects of spatial navigation. Typically, oscillatory power in brain circuits is analyzed with Fourier transforms or short-time Fourier methods, which involve assumptions about the signal that are likely not true and fail to succinctly capture potentially informative features. To avoid such assumptions, we applied a method that combines manifold discovery techniques with dynamical systems theory, namely diffusion maps and Takens’ time-delay embedding theory, that avoids limitations seen in traditional methods. This method, called diffusion mapped delay coordinates (DMDC), when applied to hippocampal signals recorded from juvenile rats freely navigating a Y-maze, replicates some outcomes seen with standard approaches and identifies age differences in dynamic states that traditional analyses are unable to detect. Thus, DMDC may serve as a suitable complement to more traditional analyses of LFPs recorded from behaving subjects that may enhance information yield.

A method to assess linear self-predictability of physiologic processes in the frequency domain: application to beat-to-beat variability of arterial compliance.

The concept of self-predictability plays a key role for the analysis of the self-driven dynamics of physiological processes displaying richness of oscillatory rhythms. While time domain measures of self-predictability, as well as time-varying and local extensions, have already been proposed and largely applied in different contexts, they still lack a clear spectral description, which would be significantly useful for the interpretation of the frequency-specific content of the investigated processes. Herein, we propose a novel approach to characterize the linear self-predictability (LSP) of Gaussian processes in the frequency domain. The LSP spectral functions are related to the peaks of the power spectral density (PSD) of the investigated process, which is represented as the sum of different oscillatory components with specific frequency through the method of spectral decomposition. Remarkably, each of the LSP profiles is linked to a specific oscillation of the process, and it returns frequency-specific measures when integrated along spectral bands of physiological interest, as well as a time domain self-predictability measure with a clear meaning in the field of information theory, corresponding to the well-known information storage, when integrated along the whole frequency axis. The proposed measure is first illustrated in a theoretical simulation, showing that it clearly reflects the degree and frequency-specific location of predictability patterns of the analyzed process in both time and frequency domains. Then, it is applied to beat-to-beat time series of arterial compliance obtained in young healthy subjects. The results evidence that the spectral decomposition strategy applied to both the PSD and the spectral LSP of compliance identifies physiological responses to postural stress of low and high frequency oscillations of the process which cannot be traced in the time domain only, highlighting the importance of computing frequency-specific measures of self-predictability in any oscillatory physiologic process.