Inter-Brain Synchronization During Sandplay Therapy: Individual Analyses

Interactions between the client (Cl) and therapist (Th) evolve therapeutic relationships in psychotherapy. An interpersonal link or therapeutic space is implicitly developed, wherein certain important elements are expressed and shared. However, neural basis of psychotherapy, especially of non-verbal modalities, have scarcely been explored. Therefore, we examined the neural backgrounds of such therapeutic alliances during sandplay, a powerful art/play therapy technique. Real-time and simultaneous measurement of hemodynamics was conducted in the prefrontal cortex (PFC) of Cl-Th pairs participating in sandplay and subsequent interview sessions through multichannel near-infrared spectroscopy. As sandplay is highly individualized, and no two sessions and products (sandtrays) are the same, we expected variation in interactive patterns in the Cl–Th pairs. Nevertheless, we observed a statistically significant correlation between the spatio-temporal patterns in signals produced by the homologous regions of the brains. During the sandplay condition, significant correlations were obtained in the lateral PFC and frontopolar (FP) regions in the real Cl-Th pairs. Furthermore, a significant correlation was observed in the FP region for the interview condition. The correlations found in our study were explained as a “remote” synchronization (i.e., unconnected peripheral oscillators synchronizing through a hub maintaining free desynchronized dynamics) between two subjects in a pair, possibly representing the neural foundation of empathy, which arises commonly in sandplay therapy (ST).

Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock

The mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

Intercellular coupling between peripheral circadian oscillators by TGF-β signaling

Coupling between cell-autonomous circadian oscillators is crucial to prevent desynchronization of cellular networks and disruption of circadian tissue functions. While neuronal oscillators within the mammalian central clock, the suprachiasmatic nucleus, couple intercellularly, coupling among peripheral oscillators is controversial and the molecular mechanisms are unknown. Using two- and three-dimensional mammalian culture models in vitro (mainly human U-2 OS cells) and ex vivo, we show that peripheral oscillators couple via paracrine pathways. We identify transforming growth factor–β (TGF-β) as peripheral coupling factor that mediates paracrine phase adjustment of molecular clocks through transcriptional regulation of core-clock genes. Disruption of TGF-β signaling causes desynchronization of oscillator networks resulting in reduced amplitude and increased sensitivity toward external zeitgebers. Our findings reveal an unknown mechanism for peripheral clock synchrony with implications for rhythmic organ functions and circadian health.

Oxytocinergic Cells of the Posterior Hypothalamic Paraventricular Nucleus Participate in the Food Entrained Clock

The mechanisms underlying food anticipatory activity is still not well understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON) and in the medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), Ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or Ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; contrasting, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

Genesis of the Master Circadian Pacemaker in Mice

The suprachiasmatic nucleus (SCN) of the hypothalamus is the central circadian clock of mammals. It is responsible for communicating temporal information to peripheral oscillators via humoral and endocrine signaling, ultimately controlling overt rhythms such as sleep-wake cycles, body temperature, and locomotor activity. Given the heterogeneity and complexity of the SCN, its genesis is tightly regulated by countless intrinsic and extrinsic factors. Here, we provide a brief overview of the development of the SCN, with special emphasis on the murine system.

THE ROLE OF CIRCADIAN REGULATION OF GHRELIN LEVELS IN PARKINSON’S DISEASE (LITERATURE REVIEW)

The paper is aimed at the analysis of the role of the circadian regulation of ghrelin levels in patients with Parkinson’s disease. Based on the literature data, patients with Parkinson’s disease have clinical fluctuations in the symptoms of the disease, manifested by the diurnal changes in motor activity, autonomic functions, sleep-wake cycle, visual function, and the efficacy of dopaminergic therapy. Biological rhythms are controlled by central and peripheral oscillators which links with dopaminergic neurotransmission – core of the pathogenesis of Parkinson`s disease. Circadian system is altered in Parkinson`s disease due to that ghrelin fluctuations may be changed. Ghrelin is potential food-entrainable oscillator because it is linked with clock genes expression. In Parkinson`s disease this hormone may induce eating behavior changing and as a result metabolic disorder. The “hunger hormone” ghrelin can be a biomarker of the Parkinson’s disease, and the study of its role in the pathogenesis, as well as its dependence on the period of the day, intake of levodopa medications to improve the effectiveness of treatment is promising.

A robust and self-sustained peripheral circadian oscillator reveals differences in temperature compensation properties with central brain clocks

Circadian clocks temporally organize physiology and behavior of organisms exposed to the daily changes of light and temperature on our planet, thereby contributing to fitness and health. Circadian clocks and the biological rhythms they control are characterized by three properties. (1) The rhythms are self-sustained in constant conditions with a period of ~ 24 hr, (2), they can be synchronized to the environmental cycles of light and temperature, and (3), they are temperature compensated, meaning they run with the same speed at different temperatures within the physiological range of the organism. Apart from the central clocks located in or near the brain, which regulate the daily activity rhythms of animals, the so-called peripheral clocks are dispersed throughout the body of insects and vertebrates. Based on the three defining properties, it has been difficult to determine if these peripheral clocks are true circadian clocks. We used a set of clock gene – luciferase reporter genes to address this question in Drosophila circadian clocks. We show that self-sustained fly peripheral oscillators over compensate temperature changes, i.e., they slow down with increasing temperature. This over-compensation is not observed in central clock neurons in the fly brain, both in intact flies and in cultured brains, suggesting that neural network properties contribute to temperature compensation. However, an important neuropeptide for synchronizing the circadian neuronal network, the Pigment Dispersing Factor (PDF), is not required for self-sustained and temperature-compensated oscillations in subsets of the central clock neurons. Our findings reveal a fundamental difference between central and peripheral clocks, which likely also applies for vertebrate clocks.

The Role of Purinergic Receptors in the Circadian System

The circadian system is an internal time-keeping system that synchronizes the behavior and physiology of an organism to the 24 h solar day. The master circadian clock, the suprachiasmatic nucleus (SCN), resides in the hypothalamus. It receives information about the environmental light/dark conditions through the eyes and orchestrates peripheral oscillators. Purinergic signaling is mediated by extracellular purines and pyrimidines that bind to purinergic receptors and regulate multiple body functions. In this review, we highlight the interaction between the circadian system and purinergic signaling to provide a better understanding of rhythmic body functions under physiological and pathological conditions.