Research using rodents in recent years has advanced our understanding of the mechanisms by which the central nervous system regulates colorectal motility and defecation. It has been demonstrated that the spinal defecation center regulates motility of the distal colon and rectum via the pelvic nerve, and that its function is modulated by multiple monoamines and peptides. In particular, evidence that a descending neural pathway, involving the hypothalamus, the medullary raphe nuclei, and the spinal defecation center, is involved in defecation induced by acute psychological stress is of significant importance. These findings provide a basis for the concept of the gut-brain axis and are also useful for understanding the mechanisms underlying stress-related defecation disorders. In this review, we summarize the multi-level regulatory mechanisms of colorectal motility and defecation, as well as the central neural circuits involved in the control of defecation during psychological stress, including our recent findings.

Parkinson’s disease (PD) is increasingly recognized not merely as a central nervous system disorder but as a systemic disease characterized by widespread α-synuclein pathology. Gastrointestinal (GI) symptoms, particularly constipation, frequently precede the onset of classic motor symptoms and significantly impair patients’ quality of life. This review outlines the pathophysiology of GI dysfunction in PD, focusing on the autonomic nervous system, neurotransmitter alterations, and the gut-brain axis. According to Braak’s hypothesis, α-synuclein pathology may originate in the enteric nervous system and propagate to the brainstem via the vagus nerve. The early involvement of lower brainstem structures, including the defecation center, provides a neuroanatomical basis for prodromal GI symptoms. Furthermore, beyond dopaminergic depletion, the early impairment of the acetylcholine (ACh) system causes peripheral parasympathetic dysfunction, which directly contributes to impaired GI motility. Clinical interventions targeting this cholinergic deficit have shown clinical promise. Our long-term randomized controlled trial demonstrated that donepezil, a cholinesterase inhibitor, safely improved not only cognitive function but also non-motor symptoms such as constipation in PD patients with severe hyposmia. Although the precise mechanisms of the gut-brain axis―whether propagation is bottom-up, top-down, or bidirectional―remain a subject of active debate, appropriate evaluation and management of early GI symptoms are crucial. Further elucidation of these pathways holds significant potential for the development of novel, gut-targeted disease-modifying therapies for PD.

The human brain oscillates in harmony with frequency-specific subcomponents of several brain regions. The heart and brain are connected bi-directionally, and heart rate variability (HRV) may reflect the activity of the coordinating system, notably brain functional connectivity, including the default mode network (DMN). As shown herein, HRV may thus inform about humans’ mind, including the well-being (e.g., satisfaction). First, the VLF component (0.003–0.04 Hz) of HRV (VLF-HRV) in healthy subjects statistically decreased by 21.9% (n=18, p<0.00001) in association with appearance of the Northern Lights, and a graded decrease in VLF-HRV was validated depending on the degree of geomagnetic activity (p<0.05). Second, we confirmed 20 astronauts’ response to space in terms of their HRV endpoints. VLF-HRV decreased by 23.2% (n=20, p<0.001) in space, and a decrease in VLF-HRV was validated depending on the degree of adaptation to microgravity in space. i.e., extent of VLF-HRV decrease was 29.7% when visiting space in 9 sufficiently adapted astronauts (p<0.05), but 12.9% in 11 poorly adapted astronauts (N.S.). VLF-HRV is known as a powerful predictor of cardiovascular disease risk, whereas it was recently noted as a representative HRV index which inversely reflects a sense of deeply impressed satisfaction related to the brain’s DMN activity. It could thus be said that an abrupt decrease in VLF-HRV could mean survival (strong happiness) or death (life threatening condition) depending on the circumstances, because from a viewpoint of functional brain’s neural networks, those outcomes are opposite sides of the same coin.