Impairment of the visuo-spatial sketch pad by left prefrontal transcranial direct current stimulation Dear Editor, One of the many possible applications of non-invasive brain stimulation is the production of “virtual lesions”, due to transient disruption of ongoing brain activity during stimulation. “Virtual le- sions” are potentially useful for elucidating the physiology of different cortical areas and are already well documented for trans- cranial magnetic stimulation (TMS) [1]. There are still few studies showing that transcranial direct-current stimulation (tDCS) might also adversely affect ongoing physiological brain processes in an acute manner [2e4]. The effects of non-invasive brain stimulation upon memory have been studied by several investigators, but few studies have used online protocols,i.e, stimulation during performance of neuro- psychological tests [5]. As an example, Andrews et al. [6] studied the simultaneous performance of an n-back task and anodal stim- ulation of the left dorsolateral prefrontal cortex (DLPFC), but did not evaluate a possible interference of tDCS with the cognitive task, since their aim was solely to use the n-back task as an addi- tional stimulus; instead, they reported an improvement in the for- ward digit span test after combined stimulation by tDCS and the n- back task. At least two studies, however, have shown beneficial ef- fects of tDCS upon memory tasks performed simultaneously with tDCS in young adults: online anodal tDCS of the left DLPFC has been shown to improve performance in working memory (WM) tests by Fregni et al. [1] and by Ohn et al. [7]. As to the possibility of interference with normal memory pro- cesses, there have been few published reports. Bogdanov et al. [2] showed that anodal right DLPFC stimulation prevented stress- induced impairment of WM, whereas Sandrini et al. [8] have shown a disruptive effect of bilateral posterior parietal cortex tDCS upon WM in young adults. In a study of the effects of fronto-temporal tDCS upon episodic memory related to emotional visual stimuli in 20 young subjects, in which tDCS was applied simultaneously with picture presentation during the encoding phase, Penolazzi et al. [3], found that left anodal stimulation increased recall of nega- tive stimuli, supposed to be mostly analyzed by the right hemi- sphere. The authors concluded that anodal left stimulation had a “defocusing” effect, i.e., it appeared to disrupt neural networks responsible for the usual encoding of emotional memories. Zwissler et al. [4] reported an increase in the number of false alarms to lure pictures in recognition memory testing when anodal left DLPFC was applied during the encoding of pictures. The authors suggested that the increased excitability of the stimulated left DLPFC led to blurring of detail memory. According to the model of WM proposed by Baddeley [9], tem- porary holding of information in WM depends on two temporary storage systems: the phonological loop (PL) and the visuo-spatial sketch pad (VSSP). PL is responsible for temporary storage of verbal material and VSSP stores visuo-spatial information over brief pe- riods of time [9]. We have recently studied the effects of online anodal tDCS in 19 older adults (7 men, mean age 71.3 years) upon WM, using two neuropsychological tests that are dependent, respectively, upon PL and VSSP of WM [9], namely the letter- number sequencing (LNS) subtest in the WAIS-IV scale and the Corsi block tapping task (CB) - forward order. All subjects were free from neurological disease, did not use any medications with action upon the central nervous system and had no intracranial metallic implants or cardiac pacemakers. The experimental proto- col was approved by the local Ethics Committee and subjects gave their written informed consent for the study. They were randomly assigned to either of 2 groups: A or B. Group A underwent an initial session of real anodal tDCS upon F3 followed, one week later, by another sham tDCS session; group B underwent the same procedure, but sham tDCS was performed first. tDCS was delivered by a custom-built electric stimulator through a saline- soaked sponge electrode with an area of 30 cm 2 held in place over F3 by a velcro strap. The cathode was positioned over the ipsi- lateral shoulder, so as to avoid unintended cathodal stimulation of other cortical areas. In each real stimulation session, tDCS was applied at 1 mA for 20 minutes and was well tolerated by all sub- jects. During both sessions, subjects performed the LNS and the CB tasks. There were no statistically significant differences between LNS performed during sham or real tDCS; the performance in the CB task, however, was significantly worse during real tDCS, irre- spective of experimental group (p < 0.01, Fig. 1). This result is interesting not only because it demonstrates yet another instance of a tDCS-induced “virtual lesion”, but also because there was a clear dissociation of the effects on a task dependent upon PL (LNS) and one which is thought to be subserved by VSSP (CB). Hanley et al. [10] have described a clinical case with the same dissociation: patient ELD was operated on due to a sub- frontal sub-arachnnoid haematoma secondary to bleeding of a right middle cerebral artery aneurisma. She complained of being unable to recognize faces of people she met after the surgery, including personal acquaintances and people who had become famous after Contents lists available at ScienceDirect Brain Stimulation journal homepage: http://www.journals.elsevier.com/brain-stimulation Brain Stimulation xxx (2016) 1e2 http://dx.doi.org/10.1016/j.brs.2016.12.010 1935-861X/© 2016 Elsevier Inc. All rights reserved. Please cite this article in press as: Alencastro AS, et al.Impairment of the visuo-spatial sketch pad by left prefrontal transcranial direct current stimulation, Brain Stimulation (2016), http://dx.doi.org/10.1016/j.brs.2016.12.010