A new study that used functional MRI (fMRI) to measure neural activity in the brains of menopausal women has found evidence of a rise in the activity of the brainstem even before the women experience hot flashes, followed by activation in the insula and prefrontal cortex that appears to be linked to the onset of the hot flash.

The study provides novel evidence of time-ordered activity within key areas of the spinothalamic tract for these endogenously generated thermal events, according to the authors, led by Vaibhav Diwadkar, PhD, associate professor, psychiatry and behavioral neurosciences, Wayne State University School of Medicine, Detroit, Michigan.

A rise in activity in the brainstem before a hot flash is a "stunning" finding, said Dr. Diwadkar in a press release from Wayne State University. "When this finding is considered along with the fact that activity in the insula only rises after the experience of the hot flash, we gain some insight on the complexity of brain mechanisms that mediate basic regulatory functions."

The study was published online in Cerebral Cortex.

"Stunning" Finding

The study included 20 healthy symptomatic postmenopausal women aged 47 to 58 years who were not taking any medication. The women reported experiencing 6 or more hot flashes a day. Hot flashes (HFs) involve feelings of intense heat surges, accompanied by sweating and cutaneous vasodilation.

Prior to fMRI, researchers covered the participants in 2 circulating water pads. The temperature of the circulating water was increased to 42°C, producing a gradual heating stimulus that has been shown to reliably induce HFs.

Researchers used blood oxygen level-dependent fMRI to study the time courses of the responses of areas of interest in the brain, including the brainstem, insula, and dorso-lateral prefrontal cortex, before and after the onset of a spontaneous HF. They used synchronously acquired skin conductance response to detect HFs.

The researchers found a rise in activity in the brainstem before the HF and subsequent activity in the insula and prefrontal cortex. "We interpret our fMRI data to suggest that the response of brainstem structures is more proximate to the physiological origins of the HF, whereas the response of cortical structures may be more associated with the phenomenological experience of the HF," write the authors. "Thus our data…provide evidence of the origins of, and interoceptive responses to, internal thermal events."

In addition to these results, the authors also noted activity in other brain regions during the HFs, including the anterior cingulate and the basal ganglia. This, said the authors, suggests "a network of forebrain cortical and striatal regions activated in response to this event."

The study also provides evidence that fMRI is sensitive to the temporal sequencing of endogenous thermal events, such as spontaneous HFs, they note.

The neurochemical mechanisms underlying HFs are not completely understood, however, although research suggests plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), the main metabolite of the norepinephrine pathway, may be involved. MHPG is significantly higher in symptomatic vs asymptomatic postmenopausal women during resting conditions and increases significantly during HFs.

Functional Relevance

However, the functional relevance of the results is "intriguing," said the authors. "Changes in brainstem areas may precede the measured onset of the HF and the response of interoceptive regions of the cortex, rendering plausible the idea that activity in deep brain stem nuclei is responsive to gradual increases in core body temperatures."

The study has several limitations, including the difficulty in precisely locating activity within the brainstem and the confines of fMRI imaging methods. There was also no clear explanation for why the study didn't detect measurable fMRI responses in other important thermo-receptive regions, such as the hypothalamus, which is heavily implicated in thermoregulation.

The researchers are exploring possibilities for integrating imaging with treatment to examine whether specific pharmacotherapies for menopause might alter regional brain responses, according to the press release.

The study was supported by a National Institutes of Health Merit Award with additional support by a National Institute of Mental Health of the National Institutes of Health award and the state of Michigan's Joseph A. Young Sr. Fund award to the Department of Psychiatry and Behavioral Neurosciences. The authors have disclosed no relevant financial relationships.

Cerebral Cortex. Published online June 19, 2013. Abstract

 

-- Pauline Anderson

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