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 ] 17 information converges cortically within t he ACC and insula. The ACC has been classically subdivided into a subgenual/pregenual affective component and a dorsal ACC/anterior middle cingulate cortex (aMCC) cognitive c omponent. Nociceptive studies across visceral-somatic stimuli elicit robust cingulate gyrus activations; visceral stimuli frequently activate pregenual and dorsal ACC, whereas noxious cutaneous stimuli more robustly activate the MCC. The dorsal ACC/aMCC is uniquely positioned for integration and is where affectively ladened information, visceral- somatic processing, motivated behavior, and cognitive control converge. Shackman, et al recently proposed this region as a critical integrator of negative affect, pain, and cognitive control. 3 3 SUGGESTED THEORETICAL NEURAL FRAMEWORK FOR HAS- TYPE ILLNESS Aberrant circuit interactions across neural systems mediating visceral- somatic perception, emotional processing/ awareness, and cognitive control serve critical roles in the neurobiology of somatosensory amplification. Cortical-subcortical- brainstem-spinal cord interactions are theorized to mediate the amplification of visceral-somatic sensations. Thus, the somatosensory cortices (S1 and S2) and insult cortex encode sensory information, such as the location and duration of pain, nausea, or itch. 34 Important cognitive processes in somatosensory amplification include negative expectation bias (ACC, OFC, insula, hippocampal formation, and brainstem); negative attentional bias (ACC, amygdala, dorsolateral prefrontal cortex); and pain catastrophizing (ACC, dorsolateral prefrontal cortex, insula). Affective processes linked to somatosensory amplification include alexithymia (ACC, insula, and amygdala) and dysphoric-anxious mood (ACC, Insula, OFC) (Figure 1). 33 Clinical correlations. While a comprehensive review of specific disorders of heightened somatic awareness are beyond the scope of this manuscript, three representative disorders of HSA with pain, itch, and nausea sensations (fibromyalgia, atopic dermatitis, and idiopathic gastroparesis, respectively) are summarized in Table 4. 31,34–36,40–49 Fibromyalgia is a condition in which there is an imbalance of the functional connectivity within the pain network and shows strengthened connectivity of relevant brain regions involved in pain processing as well as significantly reduced connectivity of areas involved in pain inhibitory modulation. 34 Relying on published consensus statements, gastroparesis is defined by the presence of dyspeptic symptoms and the documented delay in gastric emptying of ingested nutrients in the absence of gastric outlet obstruction. Traditionally, gastroparesis was thought to be characterized by anorexia and postprandial symptoms with nausea, vomiting, bloating, early satiation, and fullness. Pain was not considered to be typical and raised the question of functional dyspepsia, although it is often present with significant nausea. 35 Regardless, strong nausea has been shown to result in sustained activation in a broad network of interoceptive, limbic, somatosensory, and cognitive processing brain areas, which results in the accompanying unpleasant effect and increased attention to the sensation of nausea. 31 Finally, atopic dermatitis (AD) is an inflammatory skin condition of intense itch and scratching. Functional magnetic resonance imaging (MRI) shows a positive correlation between disease severity and activations of the anterior cingulate cortex. The latter is likely to be associated with cognition/evaluation of itch stimuli and/or the urge to scratch. Additionally, there is significantly higher activity in the basal ganglia, including the striatum, for patients with Alzheimer's disease (AD). Activation in the basal ganglia is associated with motivation and craving. An overactivity in this region could possibly explain the excessive, pathological scratching commonly seen in AD patients. Finally, the intensity of activity in motor-related regions during scratching is significantly and positively correlated with the intensity of pleasurable sensations in AD patients. This significant positive correlation suggests that scratching-induced FIGURE 1. Summary of brain areas involved in emotional, cognitive, and visceral-somatic sensations across multiple neural circuits

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