RESEARCH ARTICLE Open Access Long-term deep-TMS does not negatively affect cognitive functions in stroke and spinal cord injury patients with central neuropathic pain Priscila Mara Lorencini Selingardi 1 , Antonia Lilian de Lima Rodrigues 1 , Valquíria Aparecida da Silva 1,2 , Diego Toledo Reis Mendes Fernandes 3 , Jefferson Rosí Jr 1 , Marco Antônio Marcolin 1 , Lin T. Yeng 1 , André R. Brunoni 3,5 , Manoel J. Teixeira 1 , Ricardo Galhardoni 1,3,4 and Daniel Ciampi de Andrade 1,2,3,6* Background Conventional superficial transcranial magnetic stimula- tion (s-TMS) has been studied for the treatment of sev- eral neuropsychiatric disorders for the last two decades [1]. It entered the armamentarium against major depres- sion in the US in 2008 [2] and is currently clinically used for the relief of the non-motor symptoms of Parkinson’s disease and of chronic pain [3], as well as for the pre- operative identification of responders before implantable epidural cortical stimulation for refractory neuropathic pain [4]. During the first years of sTMS use in clinical practice, the risk of seizures was the main adverse events-related concern, and several safety guidelines were published to screen for increased risk of seizures and to mitigate its occurrence [5]. With the accumula- tion of studies attesting to the low risk of seizures after repetitive transcranial magnetic stimulation (rTMS) when recommended safety criteria are followed, the focus of safety-related preoccupations has shifted towards the po- tential long-term cognitive and behavioral effects of sTMS protocols. Because several targets of s-TMS studies play an important whole in cognitive performance [6], the excita- tion or inhibition of these cortical areas could impair the patient’s performance in certain cognitive domains. This is potentially important if one acknowledges that several neuropsychiatric disorders treated by transcranial magnetic stimulation (TMS) already have negative effects on cogni- tion as part of the disease process, thereby creating the possibility that treatment by TMS could further worsen mental symptoms already affected by the original disease process [7]. Despite these potential detrimental effects, long-term studies assessing the effects of TMS on cogni- tion have, in fact, shown that repetitive sessions of s-TMS may leave unaltered [8], or even to some extent improve, cognitive channels (executive functions in particular) in patients suffering from neuropsychiatric diseases [9]. In the last 10 years, it has become clear that some neuropsychiatric conditions respond poorly to conven- tional s-TMS [10], while others do not respond at all [11]. For instance, bipolar mood disorders, Parkinson’s- disease-related motor symptoms, and some chronic pain syndromes such as central neuropathic pain have responded poorly to s-TMS, with either short-lasting ef- fects [12] or clinically small effect sizes [10]. For these patients, new non-invasive cortical stimulation approaches have been proposed, such as deep-TMS (d-TMS). d-TMS allows for the stimulation of deeper cortical structures such as the dentate nucleus of the cerebellum [13], the insular [14] and the cingulate cortices [15], or the leg areas of the primary motor cortex [12, 16]. These structures participate in several disease processes and brain net- works, and their non-invasive functional modulation creates the possibility of treating patients who have disease conditions not previously responsive to s-TMS. In fact, several studies have assessed the effects of d- TMS on chronic neuropathic pain [15, 17], fibromyalgia [15], major depression [18], bipolar mood disorder [19], and Parkinson’s disease, thereby creating exciting potential treatment options for patients previously unresponsive to conventional s-TMS. Here, again, d-TMS has been shown to have a low risk of seizures so long as traditional safety guidelines concerning frequency and intensity of stimula- tion are followed [5, 20]. However, most current d-TMS © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. * Correspondence: ciampi.usp@gmail.com 1 Pain Center, LIM 62 Neurosurgery, Department of Neurology, University of São Paulo, São Paulo, Brazil 2 Pain Center, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil Full list of author information is available at the end of the article Selingardi et al. BMC Neurology (2019) 19:319 https://doi.org/10.1186/s12883-019-1531-z