Abstract
Persistent fatigue is a pernicious symptom in many cancer survivors. Existing treatments are limited or ineffective and often lack any underlying biologic rationale. Acupressure is emerging as a promising new intervention for persistent cancer-related fatigue; however, the underlying mechanisms of action are unknown. Our previous investigations suggested that fatigued breast cancer survivors have alterations in brain neurochemistry within the posterior insula and disturbed functional connectivity to the default mode network (DMN), as compared to non-fatigued breast cancer survivors. Here, we investigated if insula and DMN connectivity were modulated by self-administered acupressure by randomizing breast cancer survivors (n = 19) to two distinct treatments: relaxing acupressure or stimulating acupressure. All participants underwent proton magnetic resonance spectroscopy of the posterior insula and functional connectivity magnetic resonance imaging at baseline and immediately following 6 weeks of acupressure self-treatment. As compared to baseline measures, relaxing acupressure decreased posterior insula to dorsolateral prefrontal cortex connectivity, whereas stimulating acupressure enhanced this connectivity (p < 0.05 corrected). For relaxing but not stimulating acupressure, reduced connectivity was associated with sleep improvement. In addition, connectivity of the DMN to the superior colliculus was increased with relaxing acupressure and decreased with stimulating acupressure, whereas DMN connectivity to the bilateral pulvinar was increased with stimulating and decreased with relaxing acupressure (p < 0.05 corrected). These data suggest that self-administered acupressure at different acupoints has specificity in relation to their mechanisms of action in fatigued breast cancer survivors.
Highlights
There are over three million breast cancer survivors in the United States [1]
Individuals with fatigue showed greater resting connectivity between the brain’s default mode network [DMN; a constellation of brain areas involved in self-referential thinking [10, 11]] and the superior frontal gyrus, and less connectivity between the DMN and brainstem structures including the superior colliculus (SC)/periaqueductal gray (PAG)
Improvements were seen in both fatigue and sleep following treatment for the entire cohort [fatigue mean (SD) change post − pre: −1.81(1.54), p = 0.001; sleep mean (SD) change post − pre: −2.17(3.37), p = 0.014], but there were no significant differences in symptom improvements between acupressure groups
Summary
There are over three million breast cancer survivors in the United States [1]. Breast cancer survivors often report symptoms including fatigue, sleep disturbance, pain, depression, and cognitive impairment [2]. Increased levels of brain metabolites in the posterior insula in fatigued survivors may reflect altered energy reserves (Cr is a molecule involved in ATP generation) and/or heightened excitability (glutamate is an excitatory neurotransmitter), both of which might impact insular function and sensory perception leading to fatigue Consistent with this notion, we found different brain functional connectivity patterns between breast cancer survivors with and without persistent fatigue as assessed by functional connectivity magnetic resonance imaging (fcMRI) [9]. Individuals with fatigue showed greater resting connectivity between the brain’s default mode network [DMN; a constellation of brain areas involved in self-referential thinking [10, 11]] and the superior frontal gyrus (an area of the brain involved in self-awareness), and less connectivity between the DMN and brainstem structures including the superior colliculus (SC)/periaqueductal gray (PAG) Based on these results, we hypothesized that altered neurochemistry within the insula and aberrant brain connectivity to the DMN may play a role in the pathology of fatigue and potentially other symptoms in these individuals
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