Hormesis-enhanced interoceptive refocusing (HEIR): An intervention linking the periphery and center
Poster No:
827
Submission Type:
Abstract Submission
Authors:
Otto Muzik1, Timothy Mann2, John Kopchick2, Mario Yacou2, Asadur Chowdury2, Jamie Vadgama2, Daniel Bonello2, Vaibhav Diwadkar2
Institutions:
1Wayne State University, Department of Pediatrics, Detroit, MI, 2Wayne State University, Department of Psychiatry, Detroit, MI
First Author:
Co-Author(s):
Introduction:
Several behavioral techniques have sought to combine hormetic stressors with meditation. In our recent work, we have studied a specific example of Hormesis-Enhanced Interoceptive Refocusing (HEIR): the technique activates cold-stress driven sympathetic responses in combination with controlled hypocapnia, that are both yoked to interoceptive refocusing. In trained experts, HEIR leads to increased brain activity in regions associated with interoceptive control as well as in autonomic brainstem areas implicated in stress-induced analgesia¹. These effects suggest that HEIR may drive the release of endogenous cannabinoids in both the periphery and the CNS. Such release may induce feelings of euphoria, anxiolysis and a general sense of well-being. These hypotheses motivated our current multi-modal imaging study in novice volunteers. Following a 6-week training regime, we quantified HEIR-induced longitudinal changes using PET and fMRI.
Methods:
fMRI was used to investigate acute changes in brain sub-network activity in response to a sympathetic challenge, and PET/CT imaging was used with the [18F]FMPEP-d2 tracer (an inverse agonist of the CB1 receptor). Both PET/CT and fMRI data were acquired before and after the 6-week HEIR intervention. A homogenous group (age: 24-26y) group of novice healthy male volunteers participated (only males were recruited given previous studies demonstrating gender differences in brain CB1 receptor binding²). Participants were evaluated using the SCID, YMRS and Hamilton Depression Rating Scale (HAM-D17), and were free of current medical and psychiatric illness.
The 6-week guided HEIR intervention consisted of six weekly sessions that included forceful breathing, meditation and sustained cold exposure (up-to head immersion in ice bath). Between the weekly sessions, participants maintained a daily record of their self-guided conduct of a daily 10-min deep breathing/meditation session and a cold shower.
To assess the effects of repeated cold exposure on the regulation of interoceptive function by cognitive networks, a previously developed fMRI paradigm was applied designed to generate periods of mild hypothermia interspersed by periods of return to basal core body temperature³. Functional connectivity (FC) analyses were performed to assess connectomic changes in an a priori a set of brain regions associated with homeostasis, interoception and executive control.
The 6-week guided HEIR intervention consisted of six weekly sessions that included forceful breathing, meditation and sustained cold exposure (up-to head immersion in ice bath). Between the weekly sessions, participants maintained a daily record of their self-guided conduct of a daily 10-min deep breathing/meditation session and a cold shower.
To assess the effects of repeated cold exposure on the regulation of interoceptive function by cognitive networks, a previously developed fMRI paradigm was applied designed to generate periods of mild hypothermia interspersed by periods of return to basal core body temperature³. Functional connectivity (FC) analyses were performed to assess connectomic changes in an a priori a set of brain regions associated with homeostasis, interoception and executive control.
Results:
Psychiatric assessments did not identify any psychiatric symptoms in the participants. Global and regional analyses of the PET data revealed that HEIR drive substantial increases in CB1 receptor binding across the brain. This was especially notable in regions associated with executive, interoceptive and homeostatic functions including the ACC, OFC, AIC and the brainstem (Figure 1A). Notably, HEIR-driven increases in global CB1 receptor binding were significantly associated with improvements in sub-threshold depressive symptoms (Figure 1B), suggesting a compelling impact of HEIR on changing the brain's underlying biology and the relationship between these changes and mood.
HEIR also drove increased fMRI responses in the bilateral AIC and the bilateral OFC (Figure 2A), suggesting greater regional engagement evoked by sympathetic responses. Finally, FC analysis demonstrated increased connectivity between executive and interoceptive regions (Figure 2B), suggestive of improved regulation of interoceptive function.
HEIR also drove increased fMRI responses in the bilateral AIC and the bilateral OFC (Figure 2A), suggesting greater regional engagement evoked by sympathetic responses. Finally, FC analysis demonstrated increased connectivity between executive and interoceptive regions (Figure 2B), suggestive of improved regulation of interoceptive function.
Conclusions:
The practice of HEIR appears to drive phasic changes in brain cannabinoid receptor signaling and functional brain activity (evoked by sympathetic nervous responses to whole-body cooling)4. These data suggest that HEIR exerts beneficial effects by evoking a balanced interaction between autonomic responses to controlled stress (exerted in the periphery) and ancillary psychological processes that are evoked in response to the activation of such autonomic processes (at the center).
Emotion, Motivation and Social Neuroscience:
Social Neuroscience Other 1
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making 2
Keywords:
Anxiety
Behavioral Therapy
FUNCTIONAL MRI
Positron Emission Tomography (PET)
Other - cannabinoid signaling
1|2Indicates the priority used for review
Provide references using author date format
2. Laurikainen H, Tuominen L, Tikka M, Merisaari H, Armio RL, Sormunen E, Borgan F, Veronese M, Howes O, Haaparanta-Solin M, Solin O, Hietala J; METSY group. 2019. Sex difference in brain CB1 receptor availability in man. Neuroimage 184: 834-842.
3. Muzik O, Diwadkar VA. 2016. In vivo correlates of thermoregulatory defense in humans: Temporal course of sub-cortical and cortical responses assessed with fMRI. Hum Brain Mapp 37(9): 3188-202
4. Muzik, O., Baajour, S., Chowdury, A., Diwadkar, V.A., 2022. Effective connectivity of brain networks controlling human thermoregulation. Brain Struct Funct 227 (1), 299-312.