Neuroimaging of the Brain-Gut Axis: From Basic Understanding to Treatment of Functional GI Disorders

Altered reflex and perceptual responses within the brain-gut axis have emerged as a generally accepted model to explain the cardinal symptoms of functional gastrointestinal (GI) syndromes. The ability to image the living human brain with various neuroimaging modalities has greatly enhanced our ability to study these brain gut interactions in health and disease. Reflex responses within the brain-gut axis, mediated by lamina I and vagal afferents, and efferents of the autonomic nervous system, play a crucial role in the maintenance of homeostasis during physiological perturbations caused by food intake, contractile activity, and metabolic products of the enteric flora. The insular cortex plays an important role in the conscious perception of all sensations arising from the body, while the dorsal anterior cingulate cortex (dACC), with its connection to effector systems, mediates the affective response and motivational drive. The magnitude and gain of these processes is highly influenced by central arousal systems and top-down corticolimbic modulation, mediating the effect of environmental context, emotions, cognitions, and memories on perception and gut function. The majority of neuroimaging studies of the brain gut axis in humans are consistent with the model of parallel processing of afferent information in insula and dACC. Newer hypothesis driven studies, studying the differential contributions of afferent input, central arousal systems, and cortico-limbic pontine interactions have greatly contributed to our understanding of brain gut interactions in health and disease. fMRI–mediated detection of changes in the activity and connectivity of brain regions involved in these different processes by pharmacological and behavioral therapies holds great promise for the development of novel approaches to functional GI disorders. The term refers to small-diameter sensory afferent fibers terminating in lamina I of the spinal cord that innervate all of the tissues and organs of the body, including the viscera, skin, muscle, joint, and teeth. All of these fibers signal changes in the physiological condition of the body and provide the essential sensory input that is crucial for the autonomic responses that maintain homeostasis.1Craig A.D. An ascending general homeostatic afferent pathway originating in lamina I.Prog Brain Res. 1996; 107: 225-242Crossref PubMed Google Scholar The term refers to a brain network that is consistently activated in response to homeostatic afferent fiber activation. This network includes the insular and dACC, thalamic nuclei (MDvc, VMb, VMpo), and the parabrachial nucleus (PBN). Since non-painful and painful visceral and somatic stimuli, as well as emotional stimuli, can activate this network, the term “pain matrix” commonly used to describe these regions in the literature no longer seems appropriate. Several specific meanings are used for this word in common usage. First, we experience different feelings from our bodies—including satiety, abdominal pain, and discomfort which represent afferent sensory input from receptors and can be regarded as sensations (eg, visceral sensations). Second, we experience feelings associated with our ongoing emotional condition, otherwise known as mood or affective state, such as anxiety, contentment, or irascibility. We include also what we regard as homeostatic feelings, such as chilliness, achiness, or burning pain, that represent our physical condition. Third, we experience feelings associated with strong emotions elicited by social or environmental conditions, such as anger, sadness, happiness, and so on, and the evaluation of such conditions. These feelings in particular represent the awareness of our behavioral condition. The subjective experience of all of these types of feelings is completely dependent on self-awareness in humans.2Craig A.D. How do you feel? Interoception: The sense of the physiological condition of the body.Nat Rev Neurosci. 2002; 3: 655-666PubMed Google Scholar, 3Damasio A.R. The feeling of what happens: body and emotion in the making of consciousness. 1st ed. Harcourt Brace, New York, NY1999Google Scholar The term is used to describe a neurobehavioral state adapted for the attainment of a particular goal or the resolution of particular conditions as described by Rolls.4Rolls E.T. The brain and emotion. Oxford University Press, Oxford1999Google Scholar It is characterized in humans as a motivation accompanied by a characteristic feeling and autonomic sequelae. Emotional behavior may occur without awareness or without a concomitant feeling, as during unconscious emotional actions, or as in animals that do not display self-awareness. Emotions are viewed as ongoing and continuously varying events. We define these as the motivations and feelings that are associated with changes in the body’s physiological condition and with the autonomic responses and behaviors that occur in order to restore an optimal balance.2Craig A.D. How do you feel? Interoception: The sense of the physiological condition of the body.Nat Rev Neurosci. 2002; 3: 655-666PubMed Google Scholar For example, if your body is hypoglycemic, you feel hunger and you are motivated to eat. Homeostatic emotions are the background emotions that affect our energy level, our mood, and our disposition. Spinal and vagal visceral afferent input to the central nervous system plays an important role in the generation of such emotions.