Stressors related to the COVID-19 pandemic are risk factors for psychopathology, but psychosocial protective factors might play a crucial role in buffering the pathogenic effects of the outbreak.In...

Objectives: The COVID-19 pandemic and aligned social and physical distancing regulations increase the sense of uncertainty, intensifying the risk for psychopathology globally. Anxiety disorders are associated with intolerance to uncertainty. In this review we describe brain circuits and sensorimotor pathways involved in human reactions to uncertainty. We present the healthy mode of coping with uncertainty and discuss deviations from this mode.Methods: Literature search of PubMed and Google Scholar.Results: As manifestation of anxiety disorders includes peripheral reactions and negative cognitions, we suggest an integrative model of threat cognitions modulated by sensorimotor regions: “The Sensorimotor-Cognitive-Integration-Circuit.” The model emphasizes autonomic nervous system coupling with the cortex, addressing peripheral anxious reactions to uncertainty, pathways connecting cortical regions and cost-reward evaluation circuits to sensorimotor regions, filtered by the amygdala and basal ganglia. Of special interest are the ascending and descending tracts for sensory-motor crosstalk in healthy and pathological conditions. We include arguments regarding uncertainty in anxiety reactions to the pandemic and derive from our model treatment suggestions which are supported by scientific evidence. Our model is based on systematic control theories and emphasizes the role of goal conflict regulation in health and pathology. We also address anxiety reactions as a spectrum ranging from healthy to pathological coping with uncertainty, and present this spectrum as a transdiagnostic entity in accordance with recent claims and models.Conclusions: The human need for controllability and predictability suggests that anxiety disorders reactive to the pandemic's uncertainties reflect pathological disorganization of top-down bottom-up signaling and neural noise resulting from non-pathological human needs for coherence in life.

Depression, the most prevalent psychiatric disorder in the Western world, is characterized by increased negative affect (i.e., depressed mood, cost value increase) and reduced positive affect (i.e., anhedonia, reward value decrease), fatigue, loss of appetite, and reduced psychomotor activity except for cases of agitative depression. Some forms, such as post-partum depression, have a high risk for suicidal attempts. Recent studies in humans and in animal models relate major depression occurrence and reoccurrence to alterations in dopaminergic activity, in addition to other neurotransmitter systems. Imaging studies detected decreased activity in the brain reward circuits in major depression. Therefore, the location of dopamine receptors in these circuits is relevant for understanding major depression. Interestingly, in cortico–striatal–dopaminergic pathways within the reward and cost circuits, the expression of dopamine and its contribution to reward are modulated by endocannabinoid receptors. These receptors are enriched in the striosomal compartment of striatum that selectively projects to dopaminergic neurons of substantia nigra compacta and is vulnerable to stress. This review aims to show the crosstalk between endocannabinoid and dopamine receptors and their vulnerability to stress in the reward circuits, especially in corticostriatal regions. The implications for novel treatments of major depression are discussed.

To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed “the self-regulation clock” and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the “clock” circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.

Preterm infants, age-corrected for prematurity, score on average, 10 points lower on IQ tests than full-term infants tested at comparable ages. This review focuses on the potential contribution of the hypothalamus to cognitive neuro-regulatory development in preterm infants through its bidirectional neural connections with the prefrontal cortex and its neuroendocrine activity. It aims to clarify the central role of the hypothalamus in preterm high stress situations and in influencing cognitive development via its connectivity to the cerebral cortex. The review further evaluates epigenomic sensitivity to environmental inputs. Recent results suggest that an optimal range of DNA methylations (via a continuous process of decreasing levels of receptor methylations that are too high, and increasing levels that are too low) appears necessary in order to reach an adaptive level of receptor availability. Several studies have demonstrated amelioration of preterm infants’ stress while in the Newborn Intensive Care Unit (NICUs) and following discharge. The authors postulate that feedback mechanisms and correction signals are the basis for a hypothalamic homeostatic modulating function, a “hypothalamic resistance response”, which may account for the stress reduction brought about by in- and post-NICU early interventions and their results of promoting self-regulation and cognition.

In this editorial, we discuss the neurobiological processes underlying the early emergence of awareness that we term the “when” and “how” the mind comes to live inside the body. We describe an accumulative developmental process starting during embryonic life and continuing to fetal and postnatal development, of coupling of heart rate, body movements, and sleep states on the behavioral level with underlying mechanisms on the structural, functional, cellular, and molecular levels. A developmental perspective is proposed based on Perceptual Control Theory (PCT). This includes a developing sequence of modules starting from early sensing of neural intensities to early manifestation of human mindful capacities. We also address pharmacological treatments administered to preterm infants, which may interfere with this development, and highlight the need to consider this potential “side effect” of current pharmaceuticals when developing novel pharmacogenomic treatments.