Parcellation of human periaqueductal gray at 7‐T fMRI in full and empty bladder state: The foundation to study dynamic connectivity changes related to lower urinary tract functioning

Abstract

The periaqueductal gray (PAG) is a brain stem area involved in processing signals related to urine storage and voiding. The PAG is proposed to be responsible for projecting afferent information from the bladder to cortical and subcortical brain areas and acts as a relay station projecting efferent information from cortical and subcortical areas to the pons and spinal cord. Here, we use 7-Tesla functional magnetic resonance imaging to parcellate the PAG into functionally distinct clusters during a bladder filling protocol. Methods: We assess the similarity between parcellation results in empty and full bladder states and show how these parcellations can be used to create dynamic response profiles of connectivity changes between clusters as a function of bladder sensations. Results: For each of our six healthy female participants, we found that the agreement between at least one of the clusters in both states resulting from the parcellation procedure was higher than could be expected based on chance (p ≤ .05), and observed that these clusters are significantly organized in a symmetrical lateralized fashion (p ≤ .05). Correlations between clusters change significantly as a function of experienced sensations during bladder filling (p ≤ .05). Conclusions: This opens new possibilities to investigate the effects of treatments of lower urinary tract symptoms on signal processing in the PAG, as well as the investigation of disease-specific bladder filling related dynamic signal processing in this small brain structure.

Between-subject similarity of functional connectivity-based organization of the human periaqueductal gray related to autonomic processing

“…Previous research has indicated that the PAG can reliably be subdivided into distinct clusters of functional regions that can be differentiated based on resting-state functional magnetic resonance imaging (fMRI) data at 7 Tesla (T). At the withinsubject level, these clusters show a symmetrical organization and high level of similarity between empty and full bladder states (de Rijk et al, 2021), which is in line with what would be expected based on animal work.…”

“…We have previously assessed some of the known anatomical characteristics regarding anatomical organization of the PAG and have shown that resting-state fMRI based parcellations result in clustering which show symmetrical organization as well as consistency between empty and full bladder states in healthy subjects ( de Rijk et al, 2021 ). The results we report here, additionally, show that the PAG can be subdivided into distinct functional clusters with a similar spatial distribution across participants in full bladder states.…”

“…A disturbance in the neural processing of visceral sensory information might be related to this type of LUT dysfunction. Recent neuroimaging work has reported the first indications that PAG activity reflects subjective reported bladder sensations ( de Rijk et al, 2021 ). PAG activity might, therefore, offer insights into processing of visceral sensory information and could help identify alterations in interoceptive processes which might cause “false alarms” in patients with OAB.…”

A Pilot Study of the Effect of Transcutaneous Spinal Cord Stimulation on Micturition-Related Brain Activity and Lower Urinary Tract Symptoms After Stroke

“…Recent work has further identified specialized clusters in the PAG that are particularly involved in LUT control. 15,16 On the other hand, lateral frontal lobe regions such as the VLPFC are important for executive control and decision-making. 17 Indeed, the insula and the VLPFC have been implicated as the region's most consistently activated during urinary urgency in healthy volunteers in a recent test-retest experiment.…”

Cytoarchitectonic Maps of the Human Metathalamus in 3D Space

“…Since the spatial resolution of ultra-highfield fMRI has increased to the submillimeter range in recent years, more detailed studies have been become feasible including the possibility to measure laminar brain activity ( Huber et al, 2018 ; Jia et al, 2021 ) as well as identifying functional subdivisions of subcortical ( Rijk et al, 2021 ) and cortical ( Martino et al, 2015 ; Nasr et al, 2016 ) structures.…”