Tohoku J. Exp. Med., 2020 March, 250(3)

Invited Review

Imaging Brain Mechanisms of Functional Somatic Syndromes: Potential as a Biomarker?

MICHIKO KANO,1,2 LUKAS VAN OUDENHOVE,3 PATRICK DUPONT,4 TOR D. WAGER5 and SHIN FUKUDO2,6

1Sukawa Clinic, Kirari Health-Coop, Fukushima, Fukushima, Japan
2 Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
3Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium
4Laboratory for Cognitive Neurology, KU Leuven, Leuven, Belgium
5Cognitive and Affective Neuroscience Lab, Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA
6Department of Psychosomatic Medicine, Tohoku University Hospital, Sendai, Miyagi, Japan

When patients present with persistent bodily complaints that cannot be explained by a symptom-linked organic pathology (medically unexplained symptoms), they are diagnosed with ‘functional' somatic syndromes (FSS). Despite their prevalence, the management of FSS is notoriously challenging in clinical practice. This may be because FSS are heterogeneous disorders in terms of etiopathogenesis. They include patients with primarily peripheral dysfunction, primarily centrally driven somatic symptoms, and a mix of both. Brain-imaging studies, particularly data-driven pattern recognition methods using machine learning algorithms, could provide brain-based biomarkers for these clinical conditions. In this review, we provide an overview of our brain imaging data on brain-body interactions in one of the most well-known FSS, irritable bowel syndrome (IBS), and discuss the possible development of a brain-based biomarker for FSS. Anticipation of unpredictable pain, which commonly elicits fear in FSS patients, induced increased activity in brain areas associated with hypervigilance during rectal distention and non-distention conditions in IBS. This was coupled with dysfunctional inhibitory influence of the medial prefrontal cortex (mPFC) and pregenual anterior cingulate cortex (pACC) on stress regulation systems, resulting in the activated autonomic nervous system (ANS) and neuroendocrine system stimulated by corticotropin-releasing hormone (CRH). IBS subjects with higher alexithymia, a risk factor for FSS, showed stronger activity in the insula during rectal distention but reduced subjective sensitivity. Reduced top-down regulation of the ANS and CRH system by mPFC and pACC, discordance between the insula response to stimulation and subjective sensation of pain, and stronger threat responses in hypervigilance-related areas may be a candidate brain-based biomarker.

Key words —— alexithymia; brain biomarker; brain-body interaction; irritable bowel syndrome; psychosomatic medicine

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Tohoku J. Exp. Med., 2020, 250, 137-152

Correspondence: Michiko Kano, Behavioral Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

e-mail: mkano@med.tohoku.ac.jp