Innovations In Clinical Neuroscience

MAY-JUN 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 4 , N U M B E R 5 – 6 , M A Y – J U N E 2 0 1 7 ] 16 postrating activation with increasing nausea levels. These prefrontal cortical regions might support the cognitive/evaluative disruption. 31 Both S1 and S2 also demonstrated sustained postrating activation proportionate to increasing nausea sensation. Visceral balloon inflation studies elicit activation in both interoceptive and somatosensory brain regions. 31 S1 activity has been reported to be localized to a somatotopic location (ventrolateral subregion of the postcentral gyrus) consistent with the upper GI cortical representation reported in animals and humans. 31 Interestingly, lesion studies suggest that somatosensory cortices might also support interoception, and for nausea, might relate to cues from mechanoreceptors overlying the epigastrium (e.g., gastric tachyarrhythmia is increased during nausea, as s ummarized in Table 3. 3 1 FUNCTIONAL SOMATIC SYMPTOMS Patients with functional somatic s ymptoms (FSS) experience alterations of attention, anticipation, and pain memories. A poorly elucidated network of higher brain functions, previously called the "pain matrix," is now referred to as the "neuromatrix." The former was a misnomer, as the neuromatrix is active in various conscious processes, not just pain. 3 2 The insula, which shares interactions with the ACC, is another important area implicated in FSS. The insula is known to modulate pain processing and paradigms when painful stimulation is expected. Activation of the insula has been reported primarily for cutaneous pain rather than visceral pain. In patients with fibromyalgia, experiments on pain expectation demonstrated that in patients with nondermatomal somatosensory deficits, the posterior part of the insula showed hypometabolic activation. 32 The lateral nociceptive system, which includes the insula, indicated consistent hyperperfusion, whereas the ACC and the more affective motivational system did not. The increased activation in the insula might be correlated with the exaggerated expectancy of pain and attention in FSS patients. This might be correlated with the anterior part of the insula, which is associated with cognitive-affective aspects of pain. In functional somatic syndrome patients, the increased insular activation is correlated with heightened sensory coding of stimuli that are innocuously coded in healthy patients. This effect has also been shown in patients with irritable bowel syndrome. 32 Medial and posterior parts of the insula are thought to be involved in these somatosensory discriminative abilities. It is hypothesized that an increased interoception is at work and is mediated via missing inhibitory descending prefrontal input and/or continued ascending arousal. 32 The lamina I spinothalamic pathway allows for the integration of visceral- somatic information within the brainstem, thalamus, and cortex. Visceral-somatic TABLE 2. Summary of pruritus-related brain areas based on function FUNCTION BRAIN AREAS INVOLVED Affective (emotional) sensations of Itch • anterior cingulate cortex (ACC) • Insula Cognitive evaluation of itch • Dorsolateral prefrontal cortex (DLPFC): decision- making and evaluation of functioning • Precuneus (medial parietal cortex): memory retrieval, visuospatial processing, and self- awareness Sensation of itch • Claustrum (a discrete gray matter area connected to many cortical areas): analysis, comparison, and integration of sensory information Motor control/planning of scratching in response to itch • Premotor, motor, and supplementary motor areas • Cerebellum Urge to scratch/relief upon scratching • Areas of midbrain involved in reward: ventral tegmentum (VTA), substantia nigra, and nucleus accumbens (NAcc) • Insula, ACC, and striatum TABLE 3. Summary of major nausea-related brain areas BRAIN AREA FUNCTION Orbitofrontal cortex (OFC) Affective (emotional) influence of nausea, attributes to hedonic valence and interoceptive afference Perigenual anterior cingulate cortex (pgACC) Affective (emotional) influence of nausea, strongly related to emotion Dorsolateral prefrontal cortex (DLPFC) Cognitive evaluation of nausea level Primary (S1) and secondary (S2) somatosensory cortices Involved in the sensation of nausea and interoception via cues from mechanoreceptors in the upper GI system.

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