Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study

Abstract

Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related functional MRI (fMRI). Ten patients (6 women, 4 men; age: mean +/- SD = 31 +/- 11.2) were studied while spontaneously exhibiting a variety of motor and vocal tics. On the basis of synchronized video/audio recordings, fMRI activities were analysed 2 s before and at tic onset irrespective of the clinical phenomenology. We identified a brain network of paralimbic areas such as anterior cingulate and insular cortex, supplementary motor area (SMA) and parietal operculum (PO) predominantly activated before tic onset (P < 0.05, corrected for multiple comparisons). In contrast, at the beginning of tic action, significant fMRI activities were found in sensorimotor areas including superior parietal lobule bilaterally and cerebellum. The results of this study indicate that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching.

On the functional anatomy of the urge-for-action

“…Furthermore, we also obtained ALEs for the peak activations associated with the urge to tic in individuals with TS reported by Bohlhalter et al (2006). These data are presented in Figure 5, which illustrates that all four behavioral domains overlap in the region of the mid-cingulate cortex and the insular cortex of the right hemisphere.…”

“…One notable study was that reported by Hallett and colleagues, which used functional magnetic resonance imaging (fMRI) to examine brain areas activated immediately preceding the spontaneous occurrence of motor and/or vocal tics, and thus likely to be associated with the urge to tic (Bohlhalter et al, 2006). This study identified a network of brain areas that were activated immediately prior to tic onset, and, most importantly, identified the insular cortex, the anterior cingulate cortex, and the parietal operculum, which includes the secondary somatosensory cortex (SII) (Eickhoff, Amunts, Mohlberg, & Zilles, 2006), as the most likely anatomic regions responsible for the uncomfortable feelings associated with premonitory urges to tic (Bohlhalter et al, 2006). Consistent with this proposal, electrical stimulation of the insular cortex or the parietal operculum can elicit unpleasant somatosensory or visceral sensations (Augustine, 1996;Ostrowsky et al, 2002;Penfield & Faulk, 1955).…”

“…These studies have indicated that the neural mechanisms responsible for triggering of tics may in fact differ from those involved in voluntary movements (Bohlhalter et al 2006). One notable study was that reported by Hallett and colleagues, which used functional magnetic resonance imaging (fMRI) to examine brain areas activated immediately preceding the spontaneous occurrence of motor and/or vocal tics, and thus likely to be associated with the urge to tic (Bohlhalter et al, 2006).…”

“…These studies have indicated that the neural mechanisms responsible for triggering of tics may in fact differ from those involved in voluntary movements (Bohlhalter et al 2006). One notable study was that reported by Hallett and colleagues, which used functional magnetic resonance imaging (fMRI) to examine brain areas activated immediately preceding the spontaneous occurrence of motor and/or vocal tics, and thus likely to be associated with the urge to tic (Bohlhalter et al, 2006). This study identified a network of brain areas that were activated immediately prior to tic onset, and, most importantly, identified the insular cortex, the anterior cingulate cortex, and the parietal operculum, which includes the secondary somatosensory cortex (SII) (Eickhoff, Amunts, Mohlberg, & Zilles, 2006), as the most likely anatomic regions responsible for the uncomfortable feelings associated with premonitory urges to tic (Bohlhalter et al, 2006).…”

Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome

“…33 Both IMMP2L transcripts show high expression in the cerebellum, which is involved in TS pathogenesis. 34,35 Mitochondria dysfunction at the cellular level and cerebellum involvement at the anatomic level are also related to other movement disorders such as dystonia and ataxia. 36,37 It is therefore plausible that an unbalanced mitochondria function through a defective cerebellar IMMP2L may contribute to tic formation.…”