Letters to the Editor / Brain Stimulation 8 (2015) 305e309
fMRI study of behavioral reading treatment [9] found increased right hemisphere recruitment after short-term treatment, with shifts to left hemisphere perilesional areas occurring only after an additional 8 weeks of reinforcing the learned material. Similarly, in a study using audio-visual reading training of single words for 9 people with PA, 6 weeks of training resulted in improved reading speed and reduction of the length effect, similar to the current study. Also similar were the MEG results, showing increased connection strength in the left hemisphere and reduced connection strengths in the right hemisphere [10]. Here, we found functional connectivity to perilesional ventral occipitotemporal cortex increased from left frontal areas and decreased from right occipitotemporal and parietal areas after only 5 days of treatment using tDCS. This case demonstrates that tDCS may enhance behavioral treatment for alexia, allowing successful results in fewer sessions, and accelerating changes in brain activity and connectivity associated with improvement. Though behavioral treatment certainly has the power to reorganize the brain, tDCS might offer a way to accelerate that reorganization and enhance recovery of reading after brain injury. Based on the positive, albeit preliminary findings in this case, demonstrating both accelerated learning and rapid changes in brain activity and connectivity associated with good treatment outcome, we believe that further studies are warranted to examine the use of tDCS for alexia.
Supplementary data
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References [1] Lacey EH, Lott SN, Snider SF, Sperling A, Friedman RB. Multiple oral re-reading treatment for alexia: the parts may be greater than the whole. Neuropsychol Rehabil 2010;20:601e23. [2] Fridriksson J, Richardson JD, Baker JM, Rorden C. Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a doubleblind, sham-controlled study. Stroke 2011;42(3):819e21. [3] Turkeltaub PE, Goldberg EM, Postman-Caucheteux WA, et al. Alexia due to ischemic stroke of the visual word form area. Neurocase 2014;20:230e5. [4] Damasio AR, Damasio H. The anatomic basis of pure alexia. Neurology 1983; 33:1573e83. [5] Coslett HB. Acquired dyslexia. Semin Neurol 2000;20:419e26. [6] Datta A, Bansal V, Diaz J, Patel J, Reato D, Bikson M. Gyri -precise head model of transcranial DC stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimul 2009;2:201e7. [7] Dosenbach NU, Nardos B, Cohen AL, et al. Prediction of individual brain maturity using fMRI. Science 2010;329:1358e61. [8] Philipose LE, Gottesman RF, Newhart M, et al. Neural regions essential for reading and spelling of words and pseudowords. Ann Neurol 2007;62: 481e92. [9] Kurland J, Cortes CR, Wilke M, et al. Neural Mechanisms underlying learning following semantic mediation treatment in a case of phonologic alexia. Brain Imaging Behav 2008;2:147e72. [10] Woodhead ZVJ, Penny W, Barnes GR, et al. Reading therapy strengthens topedown connectivity in patients with pure alexia. Brain 2013;136: 2579e91.
Transcranial Direct Current Stimulation to Enhance Cognitive Remediation in Schizophrenia
Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.brs.2014.10.019. This study was supported by The Doris Duke Charitable Foundation (Grant 2012062), NIH/NCATS via the GeorgetowneHoward Universities Center for Clinical and Translational Sciences (KL2TR000102), and The Vernon Family Fund.
E.H. Lacey* Department of Neurology, Georgetown University, 4000 Reservoir Road, NW Building D, 165, Washington, DC 20057, USA MedStar National Rehabilitation Hospital, USA X. Jiang Department of Neuroscience, Georgetown University, USA R.B. Friedman S.F. Snider Department of Neurology, Georgetown University, USA L.C. Parra Y. Huang Department of Biomedical Engineering, City College of New York, USA P.E. Turkeltaub Department of Neurology, Georgetown University, USA MedStar National Rehabilitation Hospital, USA * Corresponding author. Department of Neurology, Georgetown University, 4000 Reservoir Road NW Building D, 165, Washington, DC 20057, USA. Tel.: þ1 202 877 1124; fax: þ1 202 726 7521. E-mail address:
[email protected]
Received 9 October 2014 Available online 26 December 2014 http://dx.doi.org/10.1016/j.brs.2014.11.012
Dear Editors, The global cognitive deficit in schizophrenia is identifiable by the first episode of psychosis, endures over time, and is large, averaging between 1 and 2 standard deviations below that of healthy control subjects [2]. Patients’ neurocognitive functioning has further been identified to be strongly related to functional capacities, including psychosocial functioning, independent living and vocational outcomes. Pharmacological interventions so far have demonstrated limited efficacy to enhance cognitive processes or circumvent cognitive impairments [6]. Over the last three decades research attention has therefore largely focused on nonpharmacological interventions, the most studied being cognitive remediation. Cognitive remediation interventions lead to improvements in cognition and day-to-day functioning in patients, however, overall effect sizes have been small-to-moderate [10]. On the basis of these modest findings, adjunctive therapies have been proposed to further ‘boost’ treatment effects. One hypothesized adjunctive strategy, which we showed in a proof of concept study to enhance effects of cognitive training in healthy adults [7]; is the combination of non-invasive brain stimulation with cognitive training (CT). Here, we report two cases where transcranial direct current stimulation (tDCS) was used in combination with CT specifically developed to target dysfunctional pre-attentive auditory processing in schizophrenia. Following 40e50 h of training [3,4]; or when augmented with weekly meta-cognitive bridging groups [5] this computerized CT program has been associated with moderate-tolarge sized improvements in auditory working memory and verbal learning skills. However, the intensity and duration of these
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Letters to the Editor / Brain Stimulation 8 (2015) 305e309
Table 1 Outcome measures at the three study time-points.
P1
P2
Baseline End training Follow-up Baseline End training Follow-up
MATRICS domain scores (Age and education adjusted Z scores)
PANSS Scale
Speed
Attent
WM
Verb Learn
Vis Learn
Reas
Soc
Positive
Negative
General Psych.
2.6 2.2 2.1 1.7 0.1 0.1
1.8 2.4 2.8 1.1 1.1 1.3
1.0 0.3 0.1 1.0 0.9 0.3
1.9 1.3 1.4 1.8 2.0 2.1
1.3 0.7 0.2 1.7 1.8 1.7
1.6 0.5 0.9 2.0 1.4 2.0
1 0.3 0.9 1.9 1.2 1.7
8 8 8 10 10 7
11 12 12 17 14 9
19 20 20 27 23 22
UPSA
IMI Total
93 95 94 83 78 81
111 109 107 66 65 65
PANSS, Positive and Negative Syndrome Scale; UPSA, University of California, San Diego, performance-based skills assessment; IMI, Intrinsic Motivation Inventory. Follow up occurred 1 month after the end of the training period.
programs may not be feasible for all patients. As repeated tDCS sessions have been shown to increase cortical excitability [1] and plasticity [9]; we hypothesized that combining active tDCS with CT would enhance treatment outcomes over a shorter treatment course. Participant 1 was a 29 year old, single, right-handed woman with predicted premorbid IQ of 94 (National Adult Reading Test) and 12 years of formal education. She had received a diagnosis of schizophrenia two years prior. Her regular medication was oral Amisulpride 400 mg daily. Participant 2 was a 31 year old, single, right-handed young man with predicted premorbid IQ of 100, with 12 years of formal education. He had a diagnosis of schizophrenia of 9 years duration. He was on regular medications of 450 mg Clozapine and 500 mg Amisulpride daily. Written informed consent was obtained from both participants prior to study commencement. All study procedures were conducted in the Mental Health and Rehabilitation Unit at Sutherland Hospital, Sydney, and the study was approved by the hospital Research Ethics Committee. Both participants completed five sessions of CT a week, to a total of 20 sessions over four weeks. CT was administered over approximately 45 min each session. Active tDCS was given for 30 min at 2 mA concurrently with CT on three sessions per week (Monday, Wednesday and Fridays), i.e. 12 of the 20 CT sessions were combined with tDCS. Participants and raters were blinded to whether active or sham tDCS was given. The anode (7 cm 5 cm) was placed at the international 10-20 system site T3 and the cathode (10 10 cm) over the right upper arm. The left temporal lobe site for anodal, excitatory tDCS stimulation was chosen for proximity to the primary auditory cortex. Performance improvement on the CT task (Auditory frequency discrimination score) was examined across the 20 sessions. Cognitive functioning, psychiatric symptomatology, day-to-day functioning, and motivation were assessed at baseline, post intervention and at 1 month follow-up. Final scores on the CT task for participant 1 were 127 and for participant 2 were 95. The results across the non-trained cognitive and other outcome measures are shown in Table 1. As can be seen in Table 1, results on the non-trained cognitive tasks for participant 1 showed moderate-to-large sized improvements on working memory, visual memory, and reasoning domains at end-intervention which were maintained at 1 month follow-up. For participant 2, a large-sized improvement in processing speed was observed at end-intervention which was maintained at follow-up and a moderate-to-large improvement in working memory was seen at follow-up. Participant 1 had overall higher motivation scores than Participant 2. Functional status (UPSA score) did not change across the intervention for both participants. Participant 2 also improved on self-rated depression and anxiety scores. Overall, this pilot intervention combining tDCS with CT was safe and well tolerated. . Large-sized cognitive improvements were achieved and maintained after a relatively shorter treatment
period, with changes of similar magnitude to those previously reported using the same CT program over a much longer or more intensive treatment [3,5]. Consistent with previous research [8]; level of motivation was important to outcomes, with participant 1 showing greater progression on the CT task and correspondingly better cognitive outcomes. Participant 2 improved in mood and anxiety symptoms and it is possible that this may have contributed to cognitive improvements; however, the improvement in participant 1 was independent of changes in mood and anxiety. These findings provide preliminary evidence in support for the use of tDCS combined with CT to enhance neurocognitive functioning in patients with chronic schizophrenia. Future controlled trials are required to establish the efficacy of this approach. The study was funded by two grants, one from the Royal Australian and New Zealand College of Psychiatrists (New Investigator Grant, 2011) and other from The St. George and Sutherland Hospital Medical Research Foundation (RM 10304). All authors declare no conflict of interest.
Aparna Menon Tarur Padinjareveettila* Jeffrey Rogersb Colleen Looa Donel Martinc a School of Psychiatry, The University of New South Wales, South Eastern Sydney Local Health Network, Sydney, Australia b
c
School of Psychology, Australian Catholic University, Sydney, Australia
The Black Dog Institute & The University of New South Wales, Sydney, Australia
* Corresponding author. The Mental Health Rehabilitation Unit, Level 1, The Sutherland Hospital, 430 The Kingsway, Caringbah, NSW 2229, Australia. Tel.: þ61 2 95408232; fax: þ61 2 95408237. E-mail address:
[email protected] (A.M. Tarur Padinjareveettil)
Received 14 November 2014 Available online 26 December 2014 http://dx.doi.org/10.1016/j.brs.2014.11.012
References [1] Alonzo A, Brassil J, Taylor JL, et al. Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. Brain Stimul 2012;5:208e13. [2] Bratti IM, Bilder RM. Neurocognitive deficits and first episode schizophrenia; characterization and course. In: Sharma T, Harvey PD, editors. The early course of schizophrenia. Oxford, UK: Oxford University Press; 2006. p. 87e110. [3] Fisher M, Holland C, Merzenich MM, Vinogradov S. Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. Am J Psychiatry 2009;166(7):805e11.
Letters to the Editor / Brain Stimulation 8 (2015) 305e309 [4] Fisher M, Loewy R, Carter C, et al. Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia. Schizophr Bull; 2014. http://dx.doi.org/10.1093/ schbul/sbt232. [5] Keefe RSE, Vinogradov S, Medalia A, et al. Feasibility and pilot efficacy results from the multisite cognitive remediation in the Schizophrenia Trials Network (CRSTN) randomized controlled trial. J Clin Psychiatry 2012; 73(7):1016e22. [6] Keefe RS, Bilder RM, Davis SM, et al. Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 2007;64(6):633e47.
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[7] Martin DM, Liu R, Alonzo A, et al. Can transcranial direct current stimulation enhance outcomes from cognitive training: a randomized controlled trial in healthy participants? Int J Neuropsychopharmacol 2013;16(9):1927e36. [8] Medalia A, Richardson R. What predicts a good response to cognitive remediation interventions? Schizophr Bull 2005;31(4):942e53. [9] Player MJ, Taylor JL, Weickert CS, et al. Increase in PAS-induced neuroplasticity after a treatment course of transcranial direct current stimulation for depression. J Affect Disord 2014;167:140e7. [10] Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry 2011;168(5):472e85.
