טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentLev Rina
SubjectDysexcitability of the Migrainous Brain: Functional
Relationship between Somatosensory and Prefrontal
Cortices
DepartmentDepartment of Medicine
Supervisor Professor David Yarnitsky
Full Thesis textFull thesis text - English Version


Abstract

Hyperexcitability characterizes the interictal migraineous brain. A major, yet unresolved, question is whether this results from sensitization of the sensory pathways, or from their disinhibition.  Two central expressions of this hyperexcitability are decreased habituation and enhanced anticipation to external sensory stimuli. In this study we explored the neurophysiological basis for these behaviors, and their interrelations. We focused at the functional relationship between the prefrontal and somatosensory cortices during pain modulation in interictal migraine as measured by pain-evoked cortical potentials.  Using a source localization analysis of these cortical potentials, we estimated the possible cortical generators involved in processing of repeated noxious heat stimuli in migraineurs, compared to healthy subjects. The research utilized two separate studies by which the neural correlates of unanticipated (uncued) and anticipated (cued), either predictable or unpredictable, trains of painful stimuli were identified.

Migraine patients, unlike healthy subjects, failed to habituate to both unanticipated and anticipated repeated noxious stimuli. The dishabituation to pain in migraineurs was expressed by greater reports of pain intensity and unpleasantness, and higher amplitudes of pain-evoked cortical potentials.  When coming to analyze sources of this phenomenon using sLORETA software, we demonstrated an abnormal pattern of cortical activity involving attenuated activation in the prefrontal cortex with concomitant increase in the activity of the somatosensory cortex in migraine patients versus healthy controls. When testing for the combination of habituation and anticipation, by presenting a repeated series of anticipated noxious stimuli, migraineurs showed the strongest dishabituating effects, i.e. enhanced pain ratings and augmented amplitudes of cortical potentials, associated with pronounced reduced activation of the prefrontal cortex and significantly increased activation of the somatosensory cortex. The altered prefrontal-somatosensory function in migraineurs was correlated with duration of migraine disease and attack frequency.

   In summary, the results of our research indicate that reduced inhibitory function of the prefrontal cortex and concordant disinhibition of the pain-related sensory cortices are the underlying mechanisms of dishabituation to pain in migraine. This pattern was further enhanced under anticipated pain conditions. Disinhibition, thus, plays a major role in migraine’s brain hyperexcitability, highlighting the role of the frontal lobe in migraine pathogenesis. Further, the correlation of disinhibition with migraine duration and longevity supports the currently evolving concept of migraine as a progressive disease.