Mantovani A, Lisanby SH, Pieraccini F, et al. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS)

Department of Neuroscience, Section of Psychiatry, Section of Neurophysiology, Postgraduate School in Applied Neurological Sciences, Siena University, Siena, Italy.
The International Journal of Neuropsychopharmacology (Impact Factor: 4.01). 03/2006; 9(1):95-100. DOI: 10.1017/S1461145705005729
Source: PubMed


There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold.

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Available from: Simone Rossi, Feb 17, 2015
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    • "Both TS and OCD are associated with hyperactivity of regional (somatosensory or orbitofrontal) cortical output neurons, as well as impaired sensorimotor gating evidenced by PPI (prepulse inhibition) deficits (Swedo et al., 1992; Breiter et al., 1996; Ziemann et al., 1997; Edgley and Lemon, 1999; Gilbert et al., 2004; Mantovani et al., 2006; Swerdlow and Sutherland, 2006; Ahmari et al., 2012). Transcranial magnetic stimulation (TMS) confirms that both disorders involve not cortical inhibition but disinhibition (Ziemann et al., 1997; Gilbert et al., 2004; Mantovani et al., 2006). Reflecting cortical hyperactivity, elevated corticostriatal glutamatergic efflux was observed in OCD (Rosenberg et al., 2000), and repetitive, optogenetic light-evoked orbitofrontal corticostriatal glutamatergic excitation of striatal MSN causes OClike behavior in mice (Ahmari et al., 2013). "
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    ABSTRACT: The brain circuits underlying tics in Tourette's syndrome (TS) are unknown but thought to involve cortico/amygdalo-striato-thalamo-cortical (CSTC) loop hyperactivity. We previously engineered a transgenic mouse "circuit model" of TS by expressing an artificial neuropotentiating transgene (encoding the cAMP-elevating, intracellular A1 subunit of cholera toxin) within a small population of dopamine D1 receptor-expressing somatosensory cortical and limbic neurons that hyperactivate cortico/amygdalostriatal glutamatergic output circuits thought to be hyperactive in TS and comorbid obsessive-compulsive (OC) disorders. As in TS, these D1CT-7 ("Ticcy") transgenic mice's tics were alleviated by the TS drugs clonidine and dopamine D2 receptor antagonists; and their chronic glutamate-excited striatal motor output was unbalanced toward hyperactivity of the motoric direct pathway and inactivity of the cataleptic indirect pathway. Here we've examined whether these mice's tics are countered by drugs that "break" sequential elements of their hyperactive cortical/amygdalar glutamatergic and efferent striatal circuit: anti-serotonoceptive and anti-noradrenoceptive corticostriatal glutamate output blockers (the serotonin 5-HT2a,c receptor antagonist ritanserin and the NE alpha-1 receptor antagonist prazosin); agmatinergic striatothalamic GABA output blockers (the presynaptic agmatine/imidazoline I1 receptor agonist moxonidine); and nigrostriatal dopamine output blockers (the presynaptic D2 receptor agonist bromocriptine). Each drug class alleviates tics in the Ticcy mice, suggesting a hyperglutamatergic CSTC "tic circuit" could exist in TS wherein cortical/amygdalar pyramidal projection neurons' glutamatergic overexcitation of both striatal output neurons and nigrostriatal dopaminergic modulatory neurons unbalances their circuit integration to excite striatothalamic output and create tics, and illuminating new TS drug strategies.
    Full-text · Article · Oct 2015 · Brain research
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    • "rTMS to the dlPFC, although successful in major depression (O'Reardon et al, 2007; Berlim et al, 2014), has shown minimal clinical benefit over sham in double-blind trials for OCD (Alonso et al, 2001; Sachdev et al, 2007). However, medial prefrontal targets appear more promising: 1 Hz rTMS of the supplementary motor area (SMA) and pre-SMA has achieved substantial symptom improvement in case reports and randomized controlled trials (Mantovani et al, 2006, 2010a, b). Likewise, with transcranial direct current stimulation, cathodal but not anodal stimulation of the SMA has been reported to improve OCD symptoms (D'Urso et al, 2015). "
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    ABSTRACT: Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of non-response to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC), and ventral striatum. These regions may constitute therapeutic targets for neuromodulation treatments, such as repetitive transcranial magnetic stimulation (rTMS). However, the neurobiological predictors and correlates of successful rTMS treatment for OCD are unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) to identify neural predictors and correlates of response to 20-30 sessions of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40 healthy controls as baseline comparators. A region of interest in the dmPFC was used to generate whole-brain functional connectivity maps pre- and post-treatment. 10 of 20 patients met response criteria (⩾50% improvement on Yale-Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at baseline. The degree of reduction in this connectivity, from pre- to post-treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline clinical and psychometric data did not predict treatment response. In summary, reductions in fronto-striatal hyperconnectivity were associated with treatment response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI studies of deep brain stimulation in OCD, but opposite to previous reports on mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in predicting response to dmPFC-rTMS in OCD.Neuropsychopharmacology accepted article preview online, 06 October 2015. doi:10.1038/npp.2015.292.
    Full-text · Article · Mar 2015 · Brain Stimulation
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    • "Mantovani et al. (2006, 2010) stimulated the supplementary motor area (SMA) with slow rTMS. In a first study the course of treatment consisted of 10 sessions and there was a significant clinical improvement and a normalization of the right hemisphere hyperexcitability (Mantovani et al., 2006). In a second study OCD patients received 1 Hz rTMS over the SMA bilaterally for 4 weeks and showed significant reduction in the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score and a normalization of the abnormal hemispheric laterality (Mantovani, Simpson, Fallon, Rossi, & Lisanby, 2010). "

    Full-text · Dataset · Feb 2015
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