This article was downloaded by: [New York University] On: 06 June 2015, At: 07:28 Publisher: Routledge Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK

Neurocase: The Neural Basis of Cognition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/nncs20

Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder a

bc

d

d

Giordano D’Urso , Andre Russowsky Brunoni , Annalisa Anastasia , Marco Micillo , Andrea d

ef

de Bartolomeis & Antonio Mantovani a

Department of Clinical Neurosciences, Anesthesiology and Pharmachoutilization, University Hospital of Naples Federico II, Naples, Italy b

Interdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil c

Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil d

Click for updates

Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy e

Department of Physiology, Pharmacology & Neuroscience, Sophie Davis School of Biomedical Education, City University of New York, New York, NY, USA f

Division of Experimental Therapeutics, Department of Psychiatry, Columbia University/ New York State Psychiatric Institute, New York, NY, USA Published online: 14 May 2015.

To cite this article: Giordano D’Urso, Andre Russowsky Brunoni, Annalisa Anastasia, Marco Micillo, Andrea de Bartolomeis & Antonio Mantovani (2015): Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder, Neurocase: The Neural Basis of Cognition, DOI: 10.1080/13554794.2015.1045522 To link to this article: http://dx.doi.org/10.1080/13554794.2015.1045522

PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions

Neurocase, 2015 http://dx.doi.org/10.1080/13554794.2015.1045522

Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder Giordano D’Ursoa*, Andre Russowsky Brunonib,c, Annalisa Anastasiad, Marco Micillod, Andrea de Bartolomeisd and Antonio Mantovanie,f a

Downloaded by [New York University] at 07:28 06 June 2015

Department of Clinical Neurosciences, Anesthesiology and Pharmachoutilization, University Hospital of Naples Federico II, Naples, Italy; bInterdisciplinary Center for Applied Neuromodulation (CINA), University Hospital, University of São Paulo, São Paulo, Brazil; c Service of Interdisciplinary Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, University of São Paulo, São Paulo, Brazil; dDepartment of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy; eDepartment of Physiology, Pharmacology & Neuroscience, Sophie Davis School of Biomedical Education, City University of New York, New York, NY, USA; fDivision of Experimental Therapeutics, Department of Psychiatry, Columbia University/New York State Psychiatric Institute, New York, NY, USA (Received 2 September 2014; accepted 18 April 2015) About one third of patients with obsessive-compulsive disorder (OCD) fail to experience significant clinical benefit from currently available treatments. Hyperactivity of the presupplementary motor area (pre-SMA) has been detected in OCD patients, but it is not clear whether it is the primary cause or a secondary compensatory mechanism in OCD pathophysiology. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique with polarity-dependent effects on motor cortical excitability. A 33-year-old woman with treatment-resistant OCD received 20 daily consecutive 2 mA/20 min tDCS sessions with the active electrode placed on the pre-SMA, according to the 10–20 EEG system, and the reference electrode on the right deltoid. The first 10 sessions were anodal, while the last 10 were cathodal. Symptoms severity was assessed using the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) severity score. In the end of anodal stimulation, OCD symptoms had worsened. Subsequent cathodal stimulation induced a dramatic clinical improvement, which led to an overall 30% reduction in baseline symptoms severity score on the Y-BOCS. Our study supports the hypothesis that pre-SMA hyperfunction might be responsible for OCD symptoms and shows that cathodal inhibitory tDCS over this area might be an option when dealing with treatment-resistant OCD. Keywords: brain stimulation; tDCS; OCD; TMS; supplementary motor area

Obsessive-compulsive disorder (OCD) is a rather common psychiatric condition, characterized by the presence of obsessions and/or compulsions, defined as unwanted, intrusive, and recurrent thoughts, urges or images (obsessions) and repetitive behaviors, or mental acts, that the individual feels driven to perform in response to an obsession or according to rules that must be applied rigidly (compulsions). It usually begins between childhood and early adulthood and has a chronic course. If not adequately treated, this disorder can lead to high levels of subjective distress and social disability. Unfortunately, about one third of patients with OCD fail to experience significant clinical benefit from first-line interventions such as pharmacotherapy with serotonin reuptake inhibitors (SRIs) or cognitive behavioral therapy (CBT) (Simpson, Huppert, Petkova, Foa, & Liebowitz, 2006). Similarly, second-line treatments, which consist of combining, augmenting, and switching strategies, may not always provide adequate relief from symptoms and carry significant side effects (Matsunaga et al., 2009; Rabinowitz, Baruch, & Barak, 2008).

*Corresponding author. Email: [email protected] © 2015 Taylor & Francis

Thus, when these strategies fail, clinicians may have to apply nonpharmacological treatments, including brain stimulation therapies (American Psychiatric Association [APA], 2007) or even, in selected and extreme cases, ablative procedures (Lopes et al., 2014). In fact, it has been proposed that OCD results from malfunctioning of cortico-striato-thalamo-cortical circuitry including the medial prefrontal cortex (i.e., supplementary motor area [SMA] and anterior cingulate cortex), the orbitofrontal cortex (OFC), and the basal ganglia (Milad & Rauch, 2012). This model informed neurosurgical approaches to OCD and resulted in effective invasive treatments as evidenced by the FDA humanitarian use approval for high-frequency deep brain stimulation in treatment-resistant cases (Greenberg et al., 2010). However, the need for noninvasive alternatives for patients who do not respond to standard treatments (e.g. SRIs or CBT) remains. Among novel therapeutic options, transcranial direct current stimulation (tDCS) has shown promising results in

Downloaded by [New York University] at 07:28 06 June 2015

2

G. D’Urso et al.

several neuropsychiatric disorders (Kuo, Paulus, & Nitsche, 2014) and has also been proposed as a potentially effective tool in treating OCD (D’Urso, Micillo, Cosentino, & Mantovani, 2014). TDCS is a noninvasive brain stimulation technique consisting in the application of a weak, direct electrical current to the cerebral cortex through flat electrodes placed on the scalp. It is classified as “anodal” or “cathodal” according to the polarity of the active electrode, which is placed over a targeted cortical region to induce a neurophysiological change. As to the neurophysiological effect, tDCS can either increase (anodal stimulation) or decrease (cathodal stimulation) motor cortex excitability (Nitsche & Paulus, 2000) and regional cerebral blood flow (Zheng, Alsop, & Schlaug, 2011). However, these effects may not translate to other cortical areas (Rahman et al., 2013) and, in fact, may be modified or even inverted according to other factors such as stimulation intensity or baseline cortical activity (Batsikadze, Moliadze, Paulus, Kuo, & Nitsche, 2013). Nonetheless, this differential polarity-dependent effect has been successfully exploited for clinical outcomes, including the treatment of depression, where the concomitant anodal stimulation of the left dorsolateral prefrontal cortex (DLPFC) and the cathodal stimulation of the right DLPFC showed a substantial antidepressant effect, consistently with the theory of an inter-hemispheric imbalance in depression pathophysiology (Brunoni et al., 2013). Here, we report the case of a patient who received 20 daily consecutive tDCS sessions for her treatment-resistant OCD symptoms.

Methods and materials Case report A 33-year-old housewife was referred to our outpatients unit for her OCD symptoms. Excluding OCD, she reported no history of other psychiatric symptoms. Her mother was also affected by OCD, with predominant fears of contamination and washing rituals. Patient’s OCD symptoms were present from late adolescence but reached a clinical level at age 27, when she started to obsessively worry about germs and to display uncontrolled washing and cleaning behaviors. She first underwent two consecutive courses of psychotherapy, one of which was a 6-month CBT, with no significant clinical improvement. Afterwards, she underwent a pharmacological treatment with paroxetine (up to 40 mg/day) and alprazolam (0.75 mg/day) that was continued for 5 months. When she came to our observation, she had spontaneously withdrawn the pharmacological therapy because of poor response. The clinical picture was extremely severe in that the patient’s entire daytime was devoted to perform complex and exhausting washing and cleaning rituals, which also involved her two children, of 6 and 8 years

of age. She even used to live (and forced her family to do the same) in two different apartments in the same building, one of which was the “dirty” one, the only place where it was possible, for example, to cook, to receive hosts, and to wear the same clothes used outside, and the other was the “clean” one, where there were the bedrooms and every single object, piece of furniture, or person was accurately disinfected before entering and where she felt compelled to carry out thorough and continuous cleaning according to rigid rules and schedules. Despite the severity of these symptoms, she had a fair insight and recognized that her behaviors were definitively excessive. Therefore, she felt terribly guilty toward her family, particularly toward her children, for the rituals that they were forced to do and the fact that this was seriously jeopardizing her relationship with them. We first prescribed clomipramine, which was gradually titrated up to 100 mg/day and kept at this dosage for 5 weeks. This led to a moderate improvement of symptoms – about 20% reduction from the pretreatment YBOCS severity score – but also to the occurrence of unbearable side effects, i.e., a 6 kg weight gain and sexual disturbances. Those side effects induced the patient to withdraw clomipramine and to refuse further pharmacological trials despite being extremely ill. At this stage, we proposed the tDCS. tDCS device Neuromodulation was carried out by an HDC stimulator (Newronika, Milan, Italy) approved by the European Union as a Class IIa medical device (Notified Body n. 0068) and found to comply with the European safety standards (EN 60601-1, EN 60601-1-2, EN 60601-1-4). tDCS procedure After providing a written informed consent, the patient received daily applications of 20 min/2 mA tDCS for 20 consecutive weekdays (Monday–Friday, 2.4 C and 0.06 C/cm2 per session, 48 C per treatment). The stimulator was connected to two 5 × 5 cm2 spongy electrodes soaked on each side in a saline solution, covered with conductive gel, and fixed over the sites of interest with a tubular net bandage. The active electrode was placed over the pre-supplementary motor area (pre-SMA), targeted using the International 10–20 EEG system and defined at 15% of the distance between inion and nasion anterior to Cz (vertex) on the sagittal midline (Mantovani et al., 2006). The reference electrode was also connected to the stimulator but placed in an extra-cephalic position on the lateral aspect of the patient’s right deltoid. The choice to apply the extra-cephalic electrode to the right rather than to the left arm was necessary to avoid the risk of jeopardizing the heart region, as it would have

Neurocase

Downloaded by [New York University] at 07:28 06 June 2015

happened had the pre-SMA/left arm montage been applied (Parazzini, Rossi, Rossi, Priori, & Ravazzani, 2013). In the first 10 sessions, the anode was used as the active electrode. Unfortunately, not only anodal tDCS failed to improve symptoms, but even made the patient’s OCD worse. For this reason, in the last 10 sessions, the polarity of the electrodes was inverted and a cathodal stimulation was performed. The other stimulation parameters remained the same throughout all treatment sessions.

Clinical measures Diagnostic and Statistical Manual of Mental Disordersfourth edition-text revision (DSM-IV-TR) OCD diagnosis was confirmed through the Structured Clinical Interviews (SCID-I and SCID-II) for DSM-IV-TR criteria (First, Spitzer, Benjamin, Gibbon, & Williams, 1997; First, Spitzer, Gibbon, & Williams, 1996). This assessment also served to exclude any Axis I and II comorbidity. At baseline and at the end of each polarity treatment course (anodal tDCS and cathodal tDCS), OCD symptoms were assessed by the Y-BOCS (Goodman et al., 1989).

Results At baseline, the patient scored 34 on the Y-BOCS. At the end of the first 10 anodal tDCS sessions, OCD symptoms worsened and the Y-BOCS severity score increased up to 38. On the contrary, the subsequent 10 cathodal tDCS sessions led to a significant clinical improvement with the Y-BOCS severity score dropping down to 24 (Figure 1). The onset of symptoms’ change was similar for the two treatments, since both the worsening and the improvement started to appear after the first four or five sessions of the corresponding treatment

Figure 1.

3

(anodal and cathodal tDCS, respectively). At the end of the tDCS treatment considered as a whole (anodal and cathodal tDCS together), we detected an overall reduction of 30% in OCD symptoms severity. As an accessory finding, we detected a trend to an increased systolic blood pressure (sBP) (mean Δ of 2 mm/Hg) and reduced heart rate (HR) (mean Δ of 3.3 bpm) after the single anodal tDCS sessions, while opposite effects were observed after the cathodal sessions (mean sBP reduction of 2.78 mm/Hg and mean HR increase of 2.44 bpm). Consistently with previous reports on the autonomic changes induced by monopolar tDCS (Santarnecchi et al., 2014), these variations did not reach clinical or statistical significance. The treatment was well tolerated, with no adverse effects reported. Furthermore, after tDCS, the patient accepted to resume the pharmacological treatment with the purpose of maintaining the clinical result obtained by means of the stimulation. Therefore, according to the patient’s preference, paroxetine was gradually reintroduced up to 40 mg/day. At a 3-month follow-up visit, our patient was on the same dose of paroxetine and her OCD symptoms’ improvement was stable (Y-BOCS severity score = 23).

Discussion Our strategy to target the pre-SMA was based upon recent findings. In particular, it has been demonstrated that the pre-SMA is hyperactive in OCD patients during performance of cognitive tasks related to attentional aspects of action control (de Wit et al., 2012; Yucel et al., 2007). However, it is not clear whether such hyperactivity is the primary cause or it may represent a secondary and compensatory mechanism in OCD pathophysiology. Following the hypothesis that there may be an impaired neural

Y-BOCS severity scores before treatment (T0), after the anodal tDCS (T1), and after the cathodal tDCS (T2).

Downloaded by [New York University] at 07:28 06 June 2015

4

G. D’Urso et al.

efficiency in OCD, we first applied excitatory tDCS (anodal), with the purpose of enhancing function of that stimulated area. Anodal tDCS failed to improve symptoms, instead was associated with a worsening of symptoms. On the contrary, the subsequent application of cathodal tDCS was clinically effective in reducing symptoms, therefore giving, at least in our clinical setting, support to the hypothesis that pre-SMA hyperfunction might be responsible for OCD symptoms. Notably, the fact that the two current directions led to opposite results (while keeping the electrodes placement unvaried) makes it difficult to interpret the observed response as due to a placebo effect. Interestingly, our results obtained with tDCS conceptually converge with previous findings reporting an improvement of OCD symptoms after inhibitory (1-Hz) repetitive transcranial magnetic stimulation (rTMS) over the pre-SMA. In three randomized shamcontrolled trials (RCTs), 1-Hz rTMS delivered to the preSMA induced a significant reduction in OCD symptoms (Gomes, Brasil-Neto, Allam, & Rodrigues de Souza, 2012; Kumar & Chadda, 2011; Mantovani, Simpson, Fallon, Rossi, & Lisanby, 2010) and induced changes in motor cortex excitability measures (Mantovani et al., 2013). Moreover, the therapeutic effect we observed was probably specific for the targeted area (pre-SMA), since nearly identical inhibitory protocols of tDCS and rTMS resulted ineffective when applied to the dorso-lateral pre-frontal cortex (Volpato et al., 2013). Remarkably, a similar topographical specificity was found also in the effect of rTMS in OCD, as a recent meta-analysis reported that the RCTs of low-frequency rTMS targeting non-DLPFC regions (i.e., OFC or SMA) achieved the best results in reducing OCD-related symptoms (Berlim et al., 2013). The evidence deriving from the results of the application of noninvasive brain stimulation techniques (i.e., rTMS and tDCS) and from neurophysiological measures of altered motor cortex excitability in OCD (Greenberg et al., 2000; Russo et al., 2014) suggests that (1) the pre-motor/motor system is abnormally hyperactive in OCD; (2) there is a pathophysiological link between such hyperexcitability and OCD symptoms; and (3) the inhibitory modulation of preSMA by means of noninvasive brain stimulation techniques might be an effective new treatment strategy. Nonetheless, to fully substantiate the clinical effect of inhibitory tDCS in OCD, we are planning a RCT on the clinical and neurobiological effects of 4-week cathodal tDCS to the pre-SMA. In conclusion, the present case report shows that tDCS is a safe and possibly effective treatment for OCD, supporting the development of future RCTs.

Acknowledgment The authors thank Dr. Roberto Acampora for his important contributions to the successful implementation of the treatment described in this article.

Disclosure statement Dr. Mantovani and Dr. Brunoni have received financial support for this study, please see the below funding paragraph. Drs. Giordano D’Urso, Annalisa Anastasia, Marco Micillo, and Andrea de Bartolomeis have no conflict of interest or financial disclosures to report.

Funding Dr. Mantovani has received support from the National Institutes of Health [R21MH091276], the International Obsessive Compulsive Disorder Foundation, the Irving Institute/Clinical Trials Office of Columbia University Medical Center, and the São Paulo Research Foundation—FAPESP. Dr. Brunoni is supported by the following grants: 2013 NARSAD Young Investigator from the Brain & Behavior Research Foundation [Grant Number 20493], 2013 FAPESP Young Researcher from the São Paulo State Foundation [Grant Number 20911-5], and National Council for Scientific and Technological Development [CNPq, Grant Number 470904].

References American Psychiatric Association. (2007). Practice guideline for the treatment of patients with obsessive-compulsive disorder. Retrieved from http://www.psych.org/psych_pract/treatg/pg/ prac_guide.cfm Batsikadze, G., Moliadze, V., Paulus, W., Kuo, M. -F., & Nitsche, M. A. (2013). Partially non-linear stimulation intensitydependent effects of direct current stimulation on motor cortex excitability in humans. The Journal of Physiology, 591, 1987–2000. doi:10.1113/jphysiol.2012.249730 Berlim, M. T., Neufeld, N. H., & Van den Eynde, F. (2013). Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): An exploratory meta-analysis of randomized and sham-controlled trials. Journal of Psychiatric Research, 47, 999–1006. doi:10.1016/j.jpsychires.2013.03.022. Brunoni, A. R., Valiengo, L., Baccaro, A., Zanão, T. A., de Oliveira, J. F., Goulart, A., & Fregni, F. (2013). The sertraline vs. electrical current therapy for treating depression clinical study: Results from a factorial, randomized, controlled trial. JAMA Psychiatry, 70, 383–391. doi:10.1001/ 2013.jamapsychiatry.32 D’Urso, G., Micillo, M., Cosentino, C., & Mantovani, A. (2014). Differential effects of anodal and cathodal tDCS over the supplementary motor area in OCD patients. Biological Psychiatry, 75, 1S–401S. de Wit, S. J., De Vries, F. E., Van der Werf, Y. D., Cath, D. C., Heslenfeld, D. J., Veltman, E. M., . . . Van den Heuvel, O. A. (2012). Presupplementary motor area hyperactivity during response inhibition: A candidate endophenotype of obsessive-compulsive disorder. American Journal of Psychiatry, 169, 1100–1108. doi:10.1176/appi.ajp.2012.12010073 First, M. B., Spitzer, R. L., Benjamin, L. S., Gibbon, M., & Williams, J. B. W. (1997). Structured clinical interview for DSM-IV axis II personality disorders (SCID-II). Washington, DC: American Psychiatric Publishing. First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1996). Structured clinical interview for the DSM-IV axis I disorders (SCID-I). Washington, DC: American Psychiatric Publishing. Gomes, P. V. O., Brasil-Neto, J. P., Allam, N., & Rodrigues de Souza, E. (2012). A randomized, double-blind trial of

Downloaded by [New York University] at 07:28 06 June 2015

Neurocase repetitive transcranial magnetic stimulation in obsessivecompulsive disorder with three-month follow-up. The Journal of Neuropsychiatry and Clinical Neurosciences, 24, 437–443. doi:10.1176/appi.neuropsych.11100242 Goodman, W. K., Price, L. H., Rasmussen, S. A., Mazure, C., Fleischmann, R. L., Hill, C. L., & Charney, D. S. (1989). The yale-brown obsessive compulsive scale. I. Development, use, and reliability. Archives of General Psychiatry, 46, 1006–1011. Greenberg, B. D., Gabriels, L. A., Malone Jr., D. A., Rezai, A. R., Friehs, G. M., Okun, M. S., . . . Nuttin, B. J. (2010). Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: Worldwide experience. Molecular Psychiatry, 15, 64–79. doi:10.1038/ mp.2008.55 Greenberg, B. D., Ziemann, U., Corá-Locatelli, G., Harmon, A., Murphy, D. L., Keel, J. C., & Wassermann, E. M. (2000). Altered cortical excitability in obsessive-compulsive disorder. Neurology, 54, 142–147. doi:10.1212/WNL.54.1.142 Kumar, N., & Chadda, R. K. (2011). Augmentation effect of repetitive transcranial magnetic stimulation over the supplementary motor cortex in treatment refractory patients with obsessive compulsive disorder. Indian J Psychiatry, 53, 340–342. doi:10.4103/0019-5545.91909 Kuo, M.-F., Paulus, W., & Nitsche, M. A. (2014). Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases. Neuroimage, 85, 948– 960. doi:10.1016/j.neuroimage.2013.05.117 Lopes, A. C., Greenberg, B. D., Canteras, M. M., Batistuzzo, M. C., Hoexter, M. Q., Gentil, A. F., & Miguel, E. C. (2014). Gamma ventral capsulotomy for obsessive-compulsive disorder: A randomized clinical trial. JAMA Psychiatry. Advance online publication. doi:10.1001/jamapsychiatry.2014.1193 Mantovani, A., Lisanby, S. H., Pieraccini, F., Ulivelli, M., Castrogiovanni, P., & Rossi, S. 2006. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette’s syndrome (TS). International Journal of Neuropsychopharmacology, 9, 95–100. Mantovani, A., Rossi, S., Bassi, B. D., Simpson, H. B., Fallon, B. A., & Lisanby, S. H. (2013). Modulation of motor cortex excitability in obsessive-compulsive disorder: An exploratory study on the relations of neurophysiology measures with clinical outcome. Psychiatry Research, 210, 1026–1032. doi:10.1016/j.psychres.2013.08.054 Mantovani, A., Simpson, H. B., Fallon, B. A., Rossi, S., & Lisanby, S. H. (2010). Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatmentresistant obsessive-compulsive disorder. International Journal of Neuropsychopharmacology, 13, 217–227. doi:10.1017/S1461145709990435 Matsunaga, H., Nagata, T., Hayashida, K., Ohya, K., Kiriike, N., & Stein, D. J. (2009). A long-term trial of the effectiveness and safety of atypical antipsychotic agents in augmenting

5

SSRI-refractory obsessive-compulsive disorder. Journal of Clinical Psychiatry, 70, 863–868. doi:10.4088/ JCP.08m04369 Milad, M. R., & Rauch, S. L. (2012). Obsessive-compulsive disorder: Beyond segregated cortico-striatal pathways. Trends in Cognitive Sciences, 16, 43–51. doi:10.1016/j. tics.2011.11.003 Nitsche, M. A., & Paulus, W. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of Physiology, 527, 633–639. doi:10.1111/tjp.2000.527.issue-3 Parazzini, M., Rossi, E., Rossi, L., Priori, A., & Ravazzani, P. (2013). Numerical estimation of the current density in the heart during transcranial direct current stimulation. Brain Stimulation, 6, 457–459. doi:10.1016/j.brs.2012.05.007 Rabinowitz, I., Baruch, Y., & Barak, Y. (2008). High-dose escitalopram for the treatment of obsessive-compulsive disorder. International Clinical Psychopharmacology, 23, 49–53. doi:10.1097/YIC.0b013e3282f0f0c5 Rahman, A., Reato, D., Arlotti, M., Gasca, F., Datta, A., Parra, L. C., & Bikson, M. (2013). Cellular effects of acute direct current stimulation: Somatic and synaptic terminal effects. The Journal of Physiology, 591, 2563–2578. doi:10.1113/ jphysiol.2012.247171 Russo, M., Naro, A., Mastroeni, C., Morgante, F., Terranova, C., Muscatello, M. R., . . . Quartarone, A. (2014). Obsessivecompulsive disorder: A “sensory-motor” problem? International Journal of Psychophysiology, 92, 74–78. doi:10.1016/j.ijpsycho.2014.02.007 Santarnecchi, E., Feurra, M., Barneschi, F., Acampa, M., Bianco, G., Cioncoloni, D., & Rossi, S. (2014). Time course of corticospinal excitability and autonomic function interplay during and following monopolar tDCS. Front Psychiatry, 21, 86. doi:10.3389/fpsyt.2014.00086 Simpson, H. B., Huppert, J. D., Petkova, E., Foa, E. B., & Liebowitz, M. R. (2006). Response versus remission in obsessive-compulsive disorder. The Journal of Clinical Psychiatry, 67, 269–276. doi:10.4088/JCP.v67 n0214 Volpato, C., Piccione, F., Cavinato, M., Duzzi, D., Schiff, S., Foscolo, L., & Venneri, A. (2013). Modulation of affective symptoms and resting state activity by brain stimulation in a treatment-resistant case of obsessive-compulsive disorder. Neurocase, 19, 360–370. doi:10.1080/13554794. 2012.667131 Yucel, M., Harrison, B. J., Wood, S. J., Fornito, A., Wellard, R. M., Pujol, J., & Pantelis, C. 2007. Functional and biochemical alterations of the medial frontal cortex in OCD. Archives of General Psychiatry, 64, 946–955. Zheng, X., Alsop, D. C., & Schlaug, G. (2011). Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow. Neuroimage, 58, 26–33. doi:10.1016/j.neuroimage.2011.06.018

Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder.

About one third of patients with obsessive-compulsive disorder (OCD) fail to experience significant clinical benefit from currently available treatmen...
191KB Sizes 0 Downloads 7 Views