Cerebellar responses evoked by nociceptive leg withdrawal reflex as revealed by event-related FMRI

The aim of the present study was to examine nociceptive leg withdrawal reflex-related areas in the human cerebellum using event-related functional brain imaging (fMRI). Knowledge about cerebellar areas involved in unconditioned limb withdrawal reflex control has some relevance in understanding data of limb withdrawal reflex conditioning studies. Sixteen healthy adult subjects participated. Nociceptive leg withdrawal reflexes were evoked by electrical stimulation of the left tibial nerve behind the medial malleolus. An event-related fMRI paradigm was applied with a total of 30 stimuli being delivered pseudorandomly during 500 consecutive MR scans. Surface electromyographic (EMG) recordings were performed from the left anterior tibial muscle. Only trials with significant reflex EMG activity were used as active events in fMRI statistical analysis. The specified contrasts compared the active event condition with rest. Leg withdrawal reflex-related areas were located within the vermis, paravermis, and lateral posterior cerebellar hemispheres bilaterally. Vermal and paravermal areas in lobules III/IV in the anterior lobe and in lobule VIII in the posterior lobe agree with the cerebellar representation of climbing and mossy fiber hindlimb afferents and voluntary leg movements. They are likely related to efferent modulation of the leg withdrawal reflex and/or sensory processing of afferent inputs from the reflex and/or the noxious stimulus. Additional activation within vermal lobule VI and hemispheral lobules VI/Crus I may be related to other pain-related processes (e.g., facial grimacing, fear, and startlelike reactions).