Increased Functional Activation of Limbic Brain Regions during Negative Emotional Processing in Migraine

Abstract

Pain is both an unpleasant sensory and emotional experience. This is highly relevant in migraine where cortical hyperexcitability in response to sensory stimuli (including pain, light, and sound) has been extensively reported. However, migraine may feature a more general enhanced response to aversive stimuli rather than being sensory-specific. To this end we used functional magnetic resonance imaging to assess neural activation in migraineurs interictaly in response to emotional visual stimuli from the International Affective Picture System. Migraineurs, compared to healthy controls, demonstrated increased neural activity in response to negative emotional stimuli. Most notably in regions overlapping in their involvement in both nociceptive and emotional processing including the posterior cingulate, caudate, amygdala, and thalamus (cluster corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no and minimal differences in response to positive and neutral emotional stimuli, respectively. These findings support the notion that migraine may feature more generalized altered cerebral processing of aversive/negative stimuli, rather than exclusively to sensory stimuli. A generalized hypersensitivity to aversive stimuli may be an inherent feature of migraine, or a consequential alteration developed over the duration of the disease. This proposed cortical-limbic hypersensitivity may form an important part of the migraine pathophysiology, including psychological comorbidity, and may represent an innate sensitivity to aversive stimuli that underpins attack triggers, attack persistence and (potentially) gradual headache chronification.

Brain Diffusion Abnormalities in Children with Tension-Type and Migraine-Type Headaches

“…These regions are involved with both pain nociception circuitry and the limbic system, which has been previously implicated in the perception of pain in adult patients with MTH at the functional, mechanistic, and electrophysiologic levels. 16,17 The involvement of TTH abnormalities, which was unexpected, indicates that diffusion abnormalities in the hippocampus and thalamus may potentially reflect enhanced pain circuitry as opposed to intrinsic pathophysiologic differences between MTH and TTH. This study is the first to describe early ADC diffusion changes in several areas involved in the limbic circuit in pediatric patients with MTH and TTH.…”

Molecular and functional PET-fMRI measures of placebo analgesia in episodic migraine: Preliminary findings

“…Episodic migraine patients offer an ideal clinical population to investigate placebo responses given that there are well described alterations in brain structure ( Dai et al, 2015 ) and in functional responses to pain ( Schwedt et al, 2014 , Russo et al, 2012 ) and emotion ( Wilcox et al, 2016 ). There is also some evidence of altered opioidergic function in migraine, in that μ-opioid receptor binding potential is reduced in the medial prefrontal cortex during a migraine attack ( DaSilva et al, 2014 ), and the capacity for pain-induced endogenous opioid release in the periaqueductal gray, a key pain modulating region, is diminished during migraine attacks ( Nascimento et al, 2014 ).…”

Subliminal (latent) processing of pain and its evolution to conscious awareness

“…Thus, unconscious process may induce a greater analgesic state when ‘rewarding’ and a greater pain state when ‘aversive’. In support of the latter, patients with migraine seem to have enhanced responsivity to aversive pictures (Wilcox et al, 2016). Taken together, interactions with our environment result in a barrage of sensory and emotional information that may contribute to unconscious processing that can drive sensitized systems (i.e., patients who have pain) or those where an evolving emotional status may be cross-sensitized to such stimuli .…”

“…Thus, subconscious emotional and sensory aversion may contribute to maintaining the pain state. For example, in migraine patients, an aversive response to negative emotional pictures has been reported (Wilcox et al, 2016); furthermore, negative responses to unpleasant odors have been reported to enhance chronic pain in a patient with neuropathic pain (Villemure et al, 2006). Conversely, in migraineurs, colors in the green wavelength diminish photophobia (Noseda et al, 2016).…”