Applied Neuropsychology: Adult ISSN: 2327-9095 (Print) 2327-9109 (Online) Journal homepage: http://www.tandfonline.com/loi/hapn21 Role of tDCS in potentiating poststroke computerized cognitive rehabilitation: Lessons learned from a case study Antonino Leo, Rosario De Luca, Margherita Russo, Antonino Naro, Placido Bramanti & Rocco S. Calabrò To cite this article: Antonino Leo, Rosario De Luca, Margherita Russo, Antonino Naro, Placido Bramanti & Rocco S. Calabrò (2015): Role of tDCS in potentiating poststroke computerized cognitive rehabilitation: Lessons learned from a case study, Applied Neuropsychology: Adult, DOI: 10.1080/23279095.2015.1027344 To link to this article: http://dx.doi.org/10.1080/23279095.2015.1027344 Published online: 27 Oct 2015. Submit your article to this journal Article views: 19 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=hapn21 Download by: [University of Sussex Library] Date: 04 December 2015, At: 02:00 APPLIED NEUROPSYCHOLOGY: ADULT 2016, VOL. 00, NO. 00, 1–5 http://dx.doi.org/10.1080/23279095.2015.1027344 Role of tDCS in potentiating poststroke computerized cognitive rehabilitation: Lessons learned from a case study Antonino Leo, Rosario De Luca, Margherita Russo, Antonino Naro, Placido Bramanti and Rocco S. Calabrò Downloaded by [University of Sussex Library] at 02:00 04 December 2015 Robotic and Behavioral Neurorehabilitation Laboratory, IRCCS Centro Neurolesi “Bonino-Pulejo,”, Messina, Italy ABSTRACT KEYWORDS Cognitive impairment after stroke is quite common and can cause important disability with a relevant impact on quality of life. Cognitive rehabilitation (CR) and related assistive technology may improve functional outcomes. A 30-year-old woman came to our research institute for an intensive CR cycle following a right parieto-temporal stroke. Because the patient was in the chronic phase, we decided to use 3 different rehabilitative protocols: (a) traditional cognitive training (TCT), (b) computerized cognitive training (CCT), and (c) CCT combined with transcranial direct stimulation (CCT plus) with a 2-week interval separating each session. Cognitive and language deficits were investigated using an ad-hoc psychometric battery at baseline (T0), post-TCT (T1), post-CCT (T2), and post–CCT plus (T3). Our patient showed the best neuropsychological improvement, with regard to attention processes and language domain, after T3. Our data showed that CCT plus should be considered a promising tool in the treatment of poststroke neuropsychological deficits. Computerized cognitive training (CCT); transcranial direct current stimulation (tDCS); young stroke Introduction Stroke in young adults is not so uncommon and often represents a diagnostic challenge (Bevan, Sharma, & Bradley, 1990; Kikuchi, Tanaka, Murai, & Tancharoen, 2014). Stroke incidence (20/100,000 to 35/100,000 per year in individuals younger than 55 years old) increased during the last few years because of a rise in the prevalence of diabetes, obesity, cardioembolic sources, and drug abuse, as well as the still high prevalence of smoking (Béjot, 2014; Chraa, Louhab, & Kissani, 2014; Ji, Schwamm, Pervez, & Singhal, 2013; Pezzini et al., 2014). Acute ischemic stroke is the most important cause of mortality and disability and remains a serious and significant global health problem (Bevan et al., 1990) that entails significant direct and indirect costs. Cognitive impairment after stroke is quite common and can cause disability with major impacts on quality of life (QoL) and independence (Cumming, Marshall, & Lazar, 2013; Pater, Coshall, Rudd, & Wolfe, 2003; Rasquin, Lodder, & Verhey, 2005; Shim, 2013). The neuropsychological profile following stroke is mainly characterized by an alteration in executive functions, with less verbal memory impairment (Sachdev, 2004), especially after a right-hemisphere stroke (Gillespie, Bowen, & Foster, 2006; Welte, 1993). Attention is widely considered to be the basis of other cognitive functions (Hyndman & Ashburn, 2003), CONTACT Rocco Salvatore Calabrò, M.D., Ph.D Italy. © 2016 Taylor & Francis salbro77@tiscali.it because its impairment can reduce cognitive productivity and plays a key role in the rehabilitation process after stroke (Barker-Collo, Feigin, Parag, Lawes, & Senior, 2009). Poststroke language deficits can include aphasia, alexia, agraphia, and acalculia (Sinanović, Mrkonjić, Zukić, Vidović, & Imamović, 2011). Moreover, poststroke depression is estimated to occur in 30% to 35% of patients during the first year, with a negative impact on rehabilitation, QoL, cognitive function, and mortality (Gbiri, Akinpelu, & Odole, 2010; Schulte-Altedorneburg & Bereczki, 2014). During the last decade, advances in the care of those who have had a stroke have been made (World Health Organization, 1989), including prevention, acute management, and recovery, with the implementation of some informatics techniques to improve cognitive recovery (Cumming et al., 2013; Kim, 2003; Loetscher & Lincoln, 2013; Majid, Lincoln, & Weyman, 2000; Nair & Lincoln, 2007; Silver, 2014; Westerberg et al., 2007). Indeed, it is possible to increase the effects of rehabilitative training by means of noninvasive brain stimulation techniques. Transcranial direct current stimulation (tDCS) is a form of noninvasive cortical stimulation that modulates cortical excitability and performance of the brain at stimulation sites via weak polarizing currents that enhance or reduce neuronal activity by affecting the IRCCS Centro Neurolesi “Bonino-Pulejo,” S. S. 113, Contrada Casazza, Messina 98124, Downloaded by [University of Sussex Library] at 02:00 04 December 2015 2 A. LEO ET AL. resting potential of the neuronal membrane (Nitsche et al., 2008). tDCS has been reported to transiently improve working memory and attention by stimulating the left dorsolateral prefrontal cortex in healthy individuals (Fregni et al., 2005; Nelson, McKinley, Golob, Warm, & Parasuraman 2014) and in patients with Parkinson disease (Boggio et al., 2006) or Alzheimer disease (Ferrucci et al., 2008). Moreover, the potential of tDCS is to optimize cognitive rehabilitation techniques and promote long-term recovery of language (Holland, & Crinion, 2012) and working memory in patients who have had a stroke (Andrews, Hoy, Enticott, Daskalakis, & Fitzgerald, 2011; Jo et al., 2009; Miniussi et al., 2008), as shown in recent studies (Kang, Kim, & Paik, 2012; Kang, Kim, Sohn, Cohen, & Paik, 2011; You, Kim, Chun, Jung, & Park, 2011). Case description A 30-year-old right-handed woman, affected by poststroke expressive aphasia with concomitant cognitive deficits, came to our observation clinic for an intensive cycle of rehabilitation. Her psychomotor development was normal and she reported graduating from secondary school. In August 2013, she was hospitalized for sudden onset of language impairment and right hemiparesis. A computed tomography (CT) scan showed a hypodense lesion in the left parieto-temporal region, and blood tests were normal with the exception of an Methylenetetrahydrofolate reductase (MTHFR) homozygosis mutation. The patient was thus treated with antiplatelets (i.e., cardioaspirin, 100 mg) and performed a conventional rehabilitative motor and speech training (i.e., three times a week for 6 months). The patient came to our neurorehabilitation research center after about 8 months from stroke onset. As the patient was in the poststroke chronic phase, we decided to treat her by using an intensive cognitive rehabilitation protocol, including three different kinds of training: 1. Traditional cognitive training (TCT), based on a face-to-face approach between the therapist and patient using paper-and-pencil tools; 2. Computerized cognitive training (CCT) by means of the Italian platform ERICA, characterized by specific computerized task-oriented exercises with progressive difficulty, regarding five peculiar cognitive domains: attention, spatial cognition, memory, verbal executive function, and nonverbal executive function; and 3. CCT combined with tDCS (CCT plus). In particular, tDCS was delivered by a BrainStim batterydriven stimulator (E.M.S., Bologna, Italy) using a pair of rubber electrodes enclosed in saline-soaked sponges. To stimulate the right superior temporal gyrus (STG), the active electrode (cathode) was placed horizontally over T8 according to the 10– 20 electroencephalogram system. The reference electrode was placed over the left shoulder, because it has been shown that the great interelectrode distance increases brain current density due to a low-current shunt across the scalp (Bikson et al., 2010). A 1 mA direct current with a fade-in/out of 8 s was delivered for 15 min for two sessions separated by 5 min. Current density was below the safety limit of 0.052 mA/cm2 (Nitsche et al., 2003). The impedance was controlled by the device itself and kept at <10 kΩ. A 2-week interval separated each training session that was articulated in five sessions weekly for 8 weeks (for a total of 40 rehabilitative sessions). Experimental conditions were kept equal across the entire rehabilitation protocol; in particular, the tDCS administration was carried out over exact conditions each day. The patient underwent a neuropsychological and clinical evaluation before (T0) and after each rehabilitative cycle. Neuropsychological status was assessed by a skilled neuropsychologist through a proper battery to investigate cognitive domains such as attention, memory, language, and executive functions. The battery included: (a) the Mini Mental State Examination (MMSE), the Attentive Matrices (AM), Trail-Making Test Parts A and B, and the Rey Auditory Verbal Learning Immediate and Recall (RAVLI, RAVLR). Moreover we used: (b) the Token Test (TT) (De Renzi, Zambolin, & Crisi, 1987), Boston Naming Test (BNT) (Kaplan, 1983), Verbal Fluency Test (VFT), and Semantic Fluency Test (SFT) to assess spontaneous speech, comprehension, and communication skills; and c) the Hamilton Rating Scale for Depression (HRS-D) and Hamilton Rating Scale for Anxiety (HRS-A) to evaluate the presence of depressive symptoms and anxiety. To assess whether a change in the individual's score (i.e., before and after each intervention) was statistically significant or not (based on how reliable the measure is), we calculated the Reliable Change Index (RCI; Heaton et al., 2001; Jacobson & Truax, 1991; Parsons, Notebaert, Shields, & Guskiewicz, 2009). This tool can assess the statistical significance of a change in an individual's score (i.e., before and after our intervention). It is defined as the change in an individual's score divided by the standard error of the difference (SEdiff) for the test being used. The boundary value for statistical significance within the RCI is �1.96 (1.96 equates to the 95% confidence interval). In other words, the difference between the two scores (pre–post) has to be at least twice the SEdiff (i.e., 1.96 times the SEdiff) to be significant. At baseline (T0), the neuropsychological evaluation showed a mild cognitive deficit (MMSE score ¼ 24.3) with a relevant impairment in auditory verbal learning Downloaded by [University of Sussex Library] at 02:00 04 December 2015 APPLIED NEUROPSYCHOLOGY: ADULT (RAVLI ¼ 38.7, RAVLR ¼ 8.2), slurred and slow speech, with a delayed response after stimuli presentation and semantic and phonemic paraphasias. The patient also showed a moderate language disorder with alterations in TT (27, 75), difficulties in understanding, inadequate responses to complex verbal commands, and difficulties in denomination (BNT ¼ 36/60) and semantic categorization with a lacking phonetic fluency (SFT ¼ 32, VFT ¼ 25). Moreover, a moderate depression (HRS-D ¼ 17) with a tendency for anxiety (HRS-A ¼ 16) was also noted. After the end of the TCT (T1), we observed a significant improvement in many items (RCI ¼ 2.3) with some exceptions that were ameliorated only after the combined rehabilitative approach (T3; Table 1). In T2, many items further improved (RCI ¼ 2), but the greatest effects were observed after CCT plus (RCI ¼ 2.6). Indeed, language items improved only after CCT plus (T3), as did depression and anxiety scores, memory, and attentive parameters. In more detail, the patient showed the best improvement in global cognitive functioning (MMSE ¼ 30) with regard to auditory verbal learning (RAVLI ¼ 42.7, RAVLR ¼ 10.2), the selective attention process (AM ¼ 72), reduction in paraphasias with better semantic and phonemic fluencies (Letter Table 1. Comparison of psychometric measures at T0, T1, T2, and T3. Domain Cognitive status Memory Immediate Recall Attention process Test MMSE T0 T1 T2 T3 24.3 28 28 30 RAVLI 38.7 38.7 38.7 42.7 RAVLR 8.2 8.2 8.2 10.2 AM 60 65 68 72 TMT-A 30 33 33 33 TMT-B 50 55 60 62 TMT B–A 20 22 22 22 Language LVF 25 25 25 28 SVF 32 32 31 37 BNT 36 40 41 50 TT 27,75 28,75 28,75 35,75 Anxiety symptoms HRS-A 16 15 7 5 Depression symptoms HRS-D 17 16 8 4 Physical function SF-36 (QoL) 90 90 100 100 Role limits–physical 90 90 100 100 Bodily pain 90 90 100 100 General health 60 65 85 90 Vitality 15 19 45 70 Social functioning 10 16 50 65 Role limits–emotional 15 15 30 50 Mental health 10 18 22 43 Note. Mean raw data are reported. Bold values refer to significant changes (i. e., the difference between the consecutive scores is at least twice the SEdiff (standard error of the difference; i.e., 1.96 times the SEdiff). MMSE ¼ Mini Mental State Examination; RAVLI ¼ Rey Auditory Verbal Learning Immediate; RAVLR ¼ Rey Auditory Verbal Learning Recall; TMT-A ¼ Trail-Making Test-Part A; TMT-B ¼ Trail-Making Test-Part B; LVF ¼ Letter Verbal Fluency; SVF ¼ Semantic Verbal Fluency; BNT ¼ Boston Naming Test; TT ¼ Token Test; HRS-A ¼ Hamilton Rating Scale for Anxiety; HRS-D ¼ Hamilton Rating Scale for Depression; SF-36 QoL ¼ Short Form-36 Quality of Life Scale. T0: baseline; T1: after traditional treatment; T2: after computerized cognitive training; T3: after combined training. 3 Verbal Fluency [LVF] ¼ 28, Semantic Verbal Fluency [SVF] ¼ 37), denomination (BNT ¼ 50), and verbal comprehension (TT ¼ 35.75) after the CCT-plus session (T3). Discussion The novelty of our report consists in the possibility to improve cognitive function in a young patient affected by stroke in the chronic phase. We believe that our patient's evident improvement in cognition, mood, and language function may be related to such an intensive personal computer rehabilitation program associated with tDCS (CCT plus). Indeed, the patient had a mild improvement after TCT, when she performed only a traditional treatment, and had a better recovery after CCT, albeit not as evident as after the CCT-plus treatment. Moreover, language skills improved only after tDCS was applied, and thus, we do not believe the improvement was only due to a cumulative treatment effect. Thus, the active combination of tDCS with computerized and more motivating tools may have been more effective in improving neuropsychological functions. Recovering language networks are dynamic and depend on multiple factors including the location of the lesion and its size, time since injury, intensity and type of the provided intervention, age at the time of injury, and handedness. It is unlikely that in our patient, factors other than the intensive rehabilitative training may have played a role in the cognitive improvement, because the stroke was in the chronic phase (i.e., after 8 months). Cognition is not a unitary concept and incorporates multiple domains: (a) attention (focusing, shifting, dividing, or sustaining attention on a particular stimulus or task); (b) executive function (planning, organizing thoughts, inhibition, control); (c) visuospatial ability (visual search, drawing, construction); (d) memory (recall and recognition of visual and verbal information); and (e) language (expressive and receptive; Cumming et al., 2013). Reducing the impact of poststroke cognitive impairment is an important goal. Rehabilitation of impaired cognitive functions is considered a standard component of medical care after acquired brain injury. Indeed, much evidence supports the effectiveness of the two major categories of techniques—traditional and computer-assisted—which are widely used in cognitive rehabilitative treatment. A computer-assisted cognitive rehabilitation (CACR) has been frequently used since it was developed by Glisky, Schacter, and Tulving (1986). De Luca et al. (2014) have suggested that CACR may be a promising methodology to optimize the rehabilitation outcomes following brain injury (vascular or not). Noninvasive brain stimulation has shown its potential to modulate Downloaded by [University of Sussex Library] at 02:00 04 December 2015 4 A. LEO ET AL. brain plasticity in humans and it is used to promote poststroke recovery. In recent years, a variety of studies have shown that tDCS had significant effects for the rehabilitation of cognitive functions in patients with brain injury (Miniussi et al., 2008). tDCS has a high potential to be routinely administered in parallel to intensive cognitive or motor training in neurological diseases in the future (Flöel, 2014). Jo et al. (2009) studied the effects of the tDCS in working memory of patients who sustained a stroke and showed an association between the methodology and improvement in working-memory performance. In a pilot study, Park, Seo, Kim, and Ko (2014) found that the combined use of the tDCS with CACR to the prefrontal cortex may provide positive effects in improving cognitive dysfunction for patients with stroke. Our data showed that CCT in addition to the tDCS should be considered as a rehabilitative tool in the treatment of some neuropsychological deficits. It is clear, however, that a multimodal approach to tDCS is required for understanding how different parameters improve the bilateral language networks necessary to enable recovery. The interhemispheric inhibition model of poststroke language plasticity posits that the activity of right-hemisphere structures may interfere with the compensatory recovery of the left-hemisphere peri-lesional area. Indeed, this approach also led to improved language functions; cathodal-tDCS applied to the right STG was more beneficial than anodal-tDCS applied to the left STG and was more beneficial than sham (You et al., 2011). Thus, we may speculate that our patient’s good response to CCT plus TDCS could depend on the site and direction of the stimulation paradigm inducing a better functional plasticity. Considering the potential benefit of these synergic interventions highlighting the pivotal role of tDCS, further studies taking into consideration large patient populations, long treatment periods, or the combination of different rehabilitation strategies are needed to confirm our promising findings. References Andrews, S. C., Hoy, K. E., Enticott, P. G., Daskalakis, Z. J., & Fitzgerald, P. B. (2011). Improving working memory: The effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex. Brain Stimulation, 4, 84–89. doi:10.1016/j. brs.2010.06.004 Barker-Collo, S., Feigin, V. L., Parag, V., Lawes, C. M., & Senior, H. (2010). Auckland Stroke Outcomes Study. Part 2: Cognition and functional outcomes 5 years post stroke. Neurology, 75, 1608–1616. doi:10.1212/wnl.0b013e318 1fb44c8 Béjot, Y., Jacquin, A., Daubail, B., Lainay, C., Janoura, S., AboaEboulé, C., & Giroud, M. (2014). Smoking status and severity of ischemic stroke. A population-based study. European Journal of Neurology, 71, 59–64. doi:10.1159/000355021 Bevan, H., Sharma, K., & Bradley, W. (1990). Stroke in young adults. Stroke, 21, 382–386. doi:10.1161/01.str.21.3.382 Bikson, M., Datta, A., Rahman, A., & Scaturro, J. (2010). Electrode montages for tDCS and weak transcranial electrical stimulation: Role of “return” electrode’s position and size. Clinical Neurophysiology, 121, 1976–1978. Boggio, P. S., Ferrucci, R., Rigonatti, S. P., Covre, P., Nitsche, M., Pascual-Leone, A., & Felipe, F. (2006). Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease. Journal of the Neurological Sciences, 249, 31–38. doi:10.1016/j.jns.2006.05.062 Chraa, M., Louhab, N., & Kissani, N. (2014). Stroke in young adults: About 128 cases. Pan African Medical Journal, 17, 37. doi:10.11604/pamj.2014.17.37.3226 Cumming, T. B., Marshall, R. S., & Lazar, R. M. (2013). Stroke, cognitive deficits, and rehabilitation: Still an incomplete picture. International Journal of Stroke, 8, 38–45. doi:10.1111/j.1747-4949.2012.00972.x De Luca, R., Calabrò, R. S., Gervasi, G., De Salvo, S., Bonanno, L., Corallo, F., . . . Bramanti, P. (2014). Is computer-assisted training effective in improving rehabilitative outcomes after brain injury? A case-control hospital-based study. Disability and Health Journal, 7, 356–360. doi:10.1016/j.dhjo.2014.04.003 De Renzi, E., Zambolin, A., & Crisi, G. (1987). The pattern of neuropsychological impairment associated with left posterior cerebral artery infarcts. Brain, 110, 1099–1116. doi:10.1093/brain/110.5.1099 Ferrucci, R., Mameli, F., Guidi, I., Mrakic-Sposta, S., Vergari, M., Marceglia, S., . . . Priori, A. (2008). Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Neurology, 71, 493–498. doi:10.1212/ 01.wnl.0000317060.43722.a3 Flöel, A. (2014). tDCS-enhanced motor and cognitive function in neurological diseases. NeuroImage, 85, 934–947. Fregni, F., Boggio, P. S., Nitsche, M., Bermpohl, F., Antal, A., Feredoes, E., . . . Pascual-Leone, A. (2005). Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Experimental Brain Research, 166, 23–30. doi:10.1007/s00221-005-2334-6 Gbiri, C. A., Akinpelu, A. O., & Odole, A. C. (2010). Prevalence, pattern and impact of depression on quality of life of stroke survivors. International Journal of Psychiatry in Clinical Practice, 14, 198–203. doi:10.3109/ 13651501003797633 Gillespie, D. C., Bowen, A., & Foster, J. K. (2006). Memory impairment following right hemisphere stroke: A comparative meta-analytic and narrative review. The Clinical Neuropsychologist, 20, 59–75. doi:10.1080/13854040500203308 Glisky, E. L., Schacter, D. L., & Tulving, E. (1986). Computer learning by memory-impaired patients: Acquisition and retention of complex knowledge. Neuropsychologia, 24, 313–328. doi:10.1016/0028-3932(86)90017-5 Heaton, R. K., Temkin, N., Dikmen, S., Avitable, N., Taylor, M. J., Marcotte, T. D., & Grant, I. (2001). Detecting change: A comparison of three neuropsychological methods, using normal and clinical samples. Archives of Clinical Neuropsychology, 16, 75–91. doi:10.1016/s0887-6177(99) 00062-1 Downloaded by [University of Sussex Library] at 02:00 04 December 2015 APPLIED NEUROPSYCHOLOGY: ADULT Holland, R., & Crinion, J. (2012). Can tDCS enhance treatment of aphasia after stroke? Aphasiology, 26, 1169–1191. doi:10.1080/02687038.2011.616925 Hyndman, D., & Ashburn, A. (2003). People with stroke living in the community: Attention deficits, balance, ADL ability and falls. Disability & Rehabilitation, 25, 817–822. doi:10.1080/0963828031000122221 Jacobson, N. S., & Truax, P. (1991). Clinical significance: A statistical approach to defining meaningful change in psychotherapy research. Journal of Consulting and Clinical Psychology, 59, 12–19. doi:10.1037//0022-006x.59.1.12 Ji, R., Schwamm, L. H., Pervez, M. A., & Singhal, A. B. (2013). Ischemic stroke and transient ischemic attack in young adults: Risk factors, diagnostic yield, neuroimaging, and thrombolysis. JAMA Neurology, 70, 51–57. doi:10.1001/ jamaneurol.2013.575 Jo, J. M., Kim, Y.-H., Ko, M.-H., Ohn, S. H., Joen, B., & Lee, K. H. (2009). Enhancing the working memory of stroke patients using tDCS. American Journal of Physical Medicine & Rehabilitation, 88, 404–409. doi:10.1097/phm.0b013e3181a0e4cb Kang, E. K., Kim, D. Y., & Paik, N. J. (2012). Transcranial direct current stimulation of the left prefrontal cortex improves attention in patients with traumatic brain injury: A pilot study. Journal of Rehabilitation Medicine, 44, 346–350. doi:10.2340/16501977-0947 Kang, E. K., Kim, Y. K., Sohn, H. M., Cohen, L. G., & Paik, N. J. (2011). Improved picture naming in aphasia patients treated with cathodal tDCS to inhibit the right Broca's homologue area. Restorative Neurology and Neuroscience, 29, 141–152. Kaplan, R. (1983). Language and science policies of new nations. Science, 221, 913. doi:10.1126/science.221.4614.913 Kikuchi, K., Tanaka, E., Murai, Y., & Tancharoen, S. (2014). Clinical trials in acute ischemic stroke. CNS Drugs, 28, 929–938. doi:10.1007/s40263-014-0199-6 Kim, V. H. (2003). Effect of computer-assisted cognitive rehabilitation program for attention training in brain injury. Journal of Korean Academy of Rehabilitation Medicine, 27, 830–839. Loetscher, T., & Lincoln, N. B. (2013). Cognitive rehabilitation for attention deficits following stroke. The Cochrane Database of Systematic Reviews, 31, CD002842. Majid, M. J., Lincoln, N. B., & Weyman, N. (2000). Cognitive rehabilitation for memory deficits following stroke. The Cochrane Database of Systematic Reviews, 3, CD002293. Miniussi, C., Cappa, S. F., Cohen, L. G., Floel, A., Fregni, F., Nitsche, M. A., … Walsh, V. (2008). Efficacy of repetitive transcranial magnetic stimulation/transcranial direct current stimulation in cognitive neurorehabilitation. Brain Stimulation, 1, 326–336. doi:10.1016/j.brs.2008.07.002 Nair, R. D., & Lincoln, N. B. (2007). Cognitive rehabilitation for memory deficits following stroke. The Cochrane Database of Systematic Reviews, 18, CD002293. Nelson, J. T., McKinley, R. A., Golob, E. J., Warm, J. S., & Parasuraman, R. (2014). Enhancing vigilance in operators with prefrontal cortex transcranial direct current stimulation (tDCS). NeuroImage, 85, 909–917. doi:10.1016/j. neuroimage.2012.11.061 Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A., … Pascual-Leone, A. (2008). Transcranial direct current stimulation: State of the art 2008. Brain Stimulation, 1, 206–223. doi:10.1016/j.brs.2008.06.004 5 Nitsche, M. A., Liebetanz, D., Lang, N., Antal, A., Tergau, F., & Paulus, W. (2003). Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clinical Neurophysiology, 114, 2220–2222. doi:10.1016/s1388-2457(03) 00235-9 Park, S. H., Seo, J. H., Kim, Y. H., & Ko, M. H. (2014). Longterm effects of transcranial direct current stimulation combined with computer-assisted cognitive training in healthy older adults. NeuroReport, 25, 122–126. doi:10.1097/wnr.0000000000000080 Parsons, T. D., Notebaert, A. J., Shields, E. W., & Guskiewicz, K. M. (2009). Application of reliable change indices to computerized neuropsychological measures of concussion. International Journal of Neuroscience, 119, 492–507. doi:10.1080/00207450802330876 Pater, M., Coshall, C., Rudd, A. G., & Wolfe, C. D. A. (2003). Natural history of cognitive impairment after stroke and factors associated with its recovery. Clinical Rehabilitation, 17, 158–166. doi:10.1191/0269215503cr596oa Pezzini, A., Grassi, M., Lodigiani, C., Gandolfo, R. C., Zini, A., DeLodovici, M. L., . . . Italian Project on Stroke in Young Adults (IPSYS) Investigators. (2014). Predictors of longterm recurrent vascular events after ischemic stroke at young age: The Italian Project on Stroke in Young Adults. Circulation, 129, 1668–1676. doi:10.1161/circulationaha. 113.005663 Rasquin, S., Lodder, J., Verhey, F. (2005). The association between psychiatric and cognitive symptoms after stroke: A prospective study. Cerebrovascular Diseases, 19, 309–316. doi:10.1159/000084499 Sachdev, P. S., Brodaty, H., Valenzuela, M. J., Lorentz, L. M., & Koschera, A. (2004). Progression of cognitive impairment in stroke patients. Neurology, 63, 1618–1623. Schulte-Altedorneburg, M., & Bereczki, D. (2014). Post-stroke depression. Orvosi Hetilap, 155, 1335–1343. doi:10.1556/ oh.2014.29968 Shim, H. (2013). Vascular cognitive impairment and poststroke cognitive deficits. Current Neurology and Neuroscience Reports, 14, 418. doi:10.1007/s11910-013-0418-4 Silver, B. (2014). Advances in stroke over the past decade. Rhode Island Medical Journal, 1, 27–30. Sinanović, O., Mrkonjić, Z., Zukić, S., Vidović, M., & Imamović, K. (2011). Post-stroke language disorders. Acta Clinica Croatica, 50, 79–94. Welte, P. O. (1993). Indices of verbal learning and memory deficits after right hemisphere stroke. Archives of Physical Medicine and Rehabilitation, 74, 631–636. doi:10.1016/ 0003-9993(93)90162-4 Westerberg, H., Jacobaeus, H., Hirvikoski, T., Clevberger, P., Östensson, M.-L., Bartfai, A., & Klingberg, T. (2007). Computerized working memory training after stroke: A pilot study. Brain Injury, 21, 21–29. doi:10.1080/ 02699050601148726 World Health Organization. (1989). Recommendations on stroke prevention, diagnosis, and therapy. Report of the WHO Task Force on Stroke and Other Cerebrovascular Disorders. Stroke, 20, 1407–1431. doi:10.1161/01.str.20.10.1407 You, D. S., Kim, D. Y., Chun, M. H., Jung, S. E., & Park, S. J. (2011). Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in sub-acute stroke patients. Brain and Language, 119, 1–5. doi:10.1016/j.bandl.2011.05.002