The impact of neuroscience on society: Cognitive enhancement in neuropsychiatric disorders and in healthy people

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 370, Issue 1677, 2015, Pages

  Sahakian, Barbara J ^a,b   Bruhl, Annette B ^a,b,c   Cook, Jennifer ^a   Killikelly, Clare ^a   Savulich, George ^a   Piercy, Thomas ^a   Hafizi, Sepehr ^a,d   Perez, Jesus ^a,e   Fernandez Egea, Emilio ^a,b   Suckling, John ^a,b   Jones, Peter B ^a,b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c UNIVERSITY OF ZURICH   (Switzerland)

^d CAMEO North Team   (United Kingdom)

^e CAMEO   (United Kingdom)

Author keywords

Cognitive enhancers; Cognitive training; Game; Neuroethics; Schizophrenia; Smart drugs

Indexed keywords

DISEASE TREATMENT; DRUG; DRUG USER; ETHICS; HEALTH CARE; LIFESTYLE; NERVOUS SYSTEM DISORDER; NEUROLOGY; PSYCHOLOGY;

NOOTROPIC AGENT;

ALZHEIMER DISEASE; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; COGNITION; COGNITIVE THERAPY; DRUG EFFECTS; FEMALE; HUMAN; MALE; NEUROCOGNITIVE DISORDERS; NEUROSCIENCE; PARKINSON DISEASE; PROCEDURES; SCHIZOPHRENIA; TRENDS; VIDEO GAME;

ALZHEIMER DISEASE; ATTENTION DEFICIT DISORDER WITH HYPERACTIVITY; COGNITION; COGNITIVE THERAPY; FEMALE; HUMANS; MALE; NEUROCOGNITIVE DISORDERS; NEUROSCIENCES; NOOTROPIC AGENTS; PARKINSON DISEASE; SCHIZOPHRENIA; VIDEO GAMES;

EID: 84938500669     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2014.0214     Document Type: Review

References (152)

1. Care Quality Commission. 2013 The safer management of controlled drugs: annual report 2012. See http://www.cqc.org.uk/sites/default/files/documents/cdar_2012.pdf (15.12.2014).
2. Boseley S. 2014 £200,000 ‘smart’ drugs seizure prompts alarm over rising UK sales. The Guardian, London, Friday 24 October 2014.
3. Presidential Commission for the Study of Bioethics. 2014 GRAY MATTERS: integrative approaches for neuroscience, ethics, and society. See http://www.bioethics.gov/sites/default/files/Gray%20Matters%20Vol%201.pdf (29.11.2014).
4. Maslen H, Faulmüller N, Savulescu J. 2014 Pharmacological cognitive enhancement—how future neuroscientific research could advance ethical debate. Front. Syst. Neurosci. 8, 107. (doi:10.3389/fnsys.2014.00107)
5. Sahakian BJ. 2014 What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev. 43, 240-258. (doi:10.1016/j.neubiorev.2014.04.002)
6. Snyder HR. 2013 Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol. Bull. 139, 81-132. (doi:10.1037/a0028727)
7. Rhodes SM, Park J, Seth S, Coghill DR. 2012 A comprehensive investigation of memory impairment in attention deficit hyperactivity disorder and oppositional defiant disorder. J. Child Psychol. Psychiatry 53, 128-137. (doi:10.1111/j.1469-7610.2011.02436.x)
8. Barch DM, Ceaser A. 2012 Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cogn. Sci. 16, 27-34. (doi:10.1016/j.tics.2011.11.015)
9. Noël X, Van der Linden M, Brevers D, Campanella S, Hanak C, Kornreich C, Verbanck P. 2012 The contribution of executive functions deficits to impaired episodic memory in individuals with alcoholism. Psychiatry Res. 198, 116-122. (doi:10.1016/j.psychres.2011.10.007)
10. Heled E, Hoofien D, Bachar E, Cooper-Kazaz R, Gur E, Ebstein R. 2014 Employing executive functions of perceptual and memory abilities in underweight and weight-restored anorexia nervosa patients. Eat Weight Disord. 19, 479-487. (doi:10.1007/s40519-014-0119-2)
11. Abramovitch A, Abramowitz JS, Mittelman A. 2013 The neuropsychology of adult obsessive-compulsive disorder: a meta-analysis. Clin. Psychol. Rev. 33, 1163-1171. (doi:10.1016/j.cpr.2013.09.004)
12. Snyder HR, Kaiser RH, Warren SL, Heller W. 2015 Obsessive-compulsive disorder is associated with broad impairments in executive function: a metaanalysis. Clin. Psychol. Sci. 3, 301-330. (doi:10.1177/2167702614534210)
13. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. 2005 Lifetime prevalence and age-ofonset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch. Gen. Psychiatry 62, 593-602. (doi:10.1001/archpsyc.62.6.593)
14. Gogtay N et al. 2004 Dynamic mapping of human cortical development during childhood through early adulthood. Proc. Natl Acad. Sci. USA 101, 8174-8179. (doi:10.1073/pnas.0402680101)
15. Beddington J et al. 2008 The mental wealth of nations. Nature 455, 1057-1060. (doi:10.1038/4551057a)
16. Gustavsson A et al. 2011 Cost of disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21, 718-779. (doi:10.1016/j.euroneuro.2011.08.008)
17. Reppermund S, Ising M, Lucae S, Zihl J. 2009 Cognitive impairment in unipolar depression is persistent and non-specific: further evidence for the final common pathway disorder hypothesis. Psychol. Med. 39, 603-614. (doi:10.1017/S003329170800411X)
18. Preiss M, Kucerova H, Lukavsky J, Stepankova H, Sos P, Kawaciukova R. 2009 Cognitive deficits in the euthymic phase of unipolar depression. Psychiatry Res. 169, 235-239. (doi:10.1016/j.psychres.2008.06.042)
19. Lewandowski KE, Cohen BM, Öngur D. 2011 Evolution of neuropsychological dysfunction during the course of schizophrenia and bipolar disorder. Psychol. Med. 41, 225-241. (doi:10.1017/S0033291710001042)
20. Robinson LJ, Thompson JM, Gallagher P, Goswami U, Young AH, Ferrier IN, Moore PB. 2006 A metaanalysis of cognitive deficits in euthymic patients with bipolar disorder. J. Affect. Disord. 93, 105-115. (doi:10.1016/j.jad.2006.02.016)
21. Shamsi S, Lau A, Lencz T, Burdick KE, DeRosse P, Brenner R, Lindenmayer J-P, Malhotra AK. 2011 Cognitive and symptomatic predictors of functional disability in schizophrenia. Schizophr. Res. 126, 257-264. (doi:10.1016/j.schres.2010.08.007)
22. Tolman AW, Kurtz MM. 2012 Neurocognitive predictors of objective and subjective quality of life in individuals with schizophrenia: a meta-analytic investigation. Schizophr. Bull. 38, 304-315. (doi:10.1093/schbul/sbq077)
23. Depp CA, Mausbach BT, Harmell AL, Savla GN, Bowie CR, Harvey PD, Patterson TL. 2012 Metaanalysis of the association between cognitive abilities and everyday functioning in bipolar disorder. Bipolar Disord. 14, 217-226. (doi:10.1111/j.1399-5618.2012.01011.x)
24. McIntyre RS, Cha DS, Soczynska JK, Woldeyohannes HO, Gallaugher LA, Kudlow P, Alsuwaidan M, Baskaran A. 2013 Cognitive deficits and functional outcomes in major depressive disorder: determinants, substrates, and treatment interventions. Depress. Anxiety 30, 515-527. (doi:10.1002/da.22063)
25. Department of Health. 2011 No health without mental health: the economic case for improving efficiency and quality in mental health. See http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_123993.pdf (29.11.2014).
26. Keshavan MS, Vinogradov S, Rumsey J, Sherrill J, Wagner A. 2014 Cognitive training in mental disorders: update and future directions. Am. J. Psychiatry 171, 510-522. (doi:10.1176/appi.ajp.2013.13081075)
27. Gestuvo MK, Hung WW. 2012 Common dietary supplements for cognitive health. Aging Health 8, 89-97. (doi:10.2217/ahe.11.92)
28. Eagger SA, Levy R, Sahakian BJ. 1991 Tacrine in Alzheimer’s disease. Lancet 337, 989-992. (doi:10.1016/0140-6736(91)92656-M)
29. de Rover M et al. 2011 Hippocampal dysfunction in patients with mild cognitive impairment: a functional neuroimaging study of a visuospatial paired associates learning task. Neuropsychologia 49, 2060-2070. (doi:10.1016/j.neuropsychologia.2011.03.037)
30. Blackwell AD, Dunn BD, Owen AM, Sahakian BJ. 2005 Neuropsychological assessment of dementia. In Dementia (eds A Burns, J O’Brien, D Ames), pp. 45-54, 3rd edn. London, UK: Hodder Arnold.
31. Howard R et al. 2012 Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N. Engl. J. Med. 366, 893-903. (doi:10.1056/NEJMoa1106668)
32. Alzheimer’s Research Trust 2014 See http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=341.
33. Getsios D, Blume S, Ishak KJ, Maclaine G, Hernandez L. 2012 An economic evaluation of early assessment for Alzheimer’s disease in the United Kingdom. Alzheimers Dement. 8, 22-30. (doi:10.1016/j.jalz.2010.07.001)
34. Lim SY, Lang AE. 2010 The nonmotor symptoms of Parkinson’s disease-an overview. Mov. Disord. 25(Suppl. 1), S123-S130. (doi:10.1002/mds.22786)
35. Parkinson’s UK. What is Parkinson’s? http://www.parkinsons.org.uk/content/what-parkinsons. (29.11.2014).
36. Hely MA, Morris JG, Reid WG, Trafficante R. 2005 Sydney Multicenter Study of Parkinson’s disease: non-L-DOPA-responsive problems dominate at 15 years. Mov. Disord. 20, 190-199. (doi:10.1002/mds.20324)
37. Seppi K et al. 2011 The movement disorder society evidence-based medicine review update: treatments for the non-motor symptoms of Parkinson’s disease. Mov. Disord. 26(Suppl. 3), S42-S80. (doi:10.1002/mds.23884)
38. Mendonca DA, Menezes K, Jog MS. 2007 Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial. Mov. Disord. 22, 2070-2076. (doi:10.1002/mds.21656)
39. Lou JS, Dimitrova DM, Park BS, Johnson SC, Eaton R, Arnold G, Nutt JG. 2009 Using modafinil to treat fatigue in Parkinson disease: a double-blind, placebo-controlled pilot study. Clin. Neuropharmacol. 32, 305-310. (doi:10.1097/WNF.0b013e3181aa916a)
40. Tyne HL, Taylor J, Baker GA, Steiger MJ. 2010 Modafinil for Parkinson’s disease fatigue. J. Neurol. 257, 452-456. (doi:10.1007/s00415-009-5351-8)
41. Cilia R, van Eimeren T. 2011 Impulse control disorders in Parkinson’s disease: seeking a roadmap toward a better understanding. Brain Struct. Funct. 216, 289-299. (doi:10.1007/s00429-011-0314-0)
42. Thomas A, Bonanni L, Gambi F, Di Iorio A, Onofrj M. 2010 Pathological gambling in Parkinson disease is reduced by amantadine. Ann. Neurol. 68, 400-404. (doi:10.1002/ana.22029)
43. Kehagia AA, Housden CR, Regenthal R, Barker RA, Muller U, Rowe J, Sahakian BJ, Robbins TW. 2014 Targeting impulsivity in Parkinson’s disease using atomoxetine. Brain 137, 1986-1997. (doi:10.1093/brain/awu117)
44. Ludolph AG et al. 2010 Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations. Br. J. Pharmacol. 160, 283-291. (doi:10.1111/j.1476-5381.2010.00707.x)
45. Manes F, Sahakian B, Clark L, Rogers R, Antoun N, Aitken M, Robbins T. 2002 Decision-making processes following damage to the prefrontal cortex. Brain 125, 624-639. (doi:10.1093/brain/awf049)
46. Ye Z et al. 2015 Improving response inhibition in Parkinson’s disease with atomoxetine. Biol. Psychiatry 77, 740-748. (doi:10.1016/j.biopsych.2014.01.024)
47. Weintraub D et al. 2010 Atomoxetine for depression and other neuropsychiatric symptoms in Parkinson disease. Neurology 75, 448-455. (doi:10.1212/WNL.0b013e3181ebdd79)
48. Marsh L, Biglan K, Gerstenhaber M, Williams JR. 2009 Atomoxetine for the treatment of executive dysfunction in Parkinson’s disease: a pilot openlabel study. Mov. Disord. 24, 277-282. (doi:10.1002/mds.22307)
49. Freitag C, Rohde L, Lempp T, Romanos M. 2010 Phenotypic and measurement influences on heritability estimates in childhood ADHD. Eur. Child Adolesc. Psychiatry 19, 311-323. (doi:10.1007/s00787-010-0097-5)
50. Posthuma D, Polderman TJ. 2013 What have we learned from recent twin studies about the etiology of neurodevelopmental disorders? Curr. Opin. Neurol. 26, 111-121. (doi:10.1097/WCO.0b013e32835f19c3)
51. Wittchen HU et al. 2011 The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21, 655-679. (doi:10.1016/j.euroneuro.2011.07.018)
52. Kessler RC, Adler LA, Barkley R, Biederman J, Conners CK, Greenhill LL, Spencer T. 2011 The prevalence and correlates of adult ADHD. In ADHD in adults: characterization, diagnosis, and treatment (eds K Jan, CC Kan, P Asherson), pp. 9-17. Cambridge, UK: Cambridge University Press.
53. Shaw M, Hodgkins P, Caci H, Young S, Kahle J, Woods AG, Arnold LE. 2010 A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and nontreatment. BMC Med. 10, 99. (doi:10.1186/1741-7015-10-99)
54. Gobbo MA, Louza MR. 2014 Influence of stimulant and non-stimulant drug treatment on driving performance in patients with attention deficit hyperactivity disorder: a systematic review. Eur. Neuropsychopharmacol. 24, 1425-1443. (doi:10.1016/j.euroneuro.2014.06.006)
55. Langberg J, Becker S. 2012 Does long-term medication use improve the academic outcomes of youth with attention-deficit/hyperactivity disorder? Clin. Child Fam. Psychol. Rev. 15, 215-233. (doi:10.1007/s10567-012-0117-8)
56. Spencer T, Biederman J. 2011 Stimulant treatment of adult ADHD. In ADHD in adults: characterization, diagnosis, and treatment (eds KB Jan, CC Kan, P Asherson), pp. 191-197. Cambridge, UK: Cambridge University Press.
57. Robinson TE, Becker JB. 1986 Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res. 396, 157-198. (doi:10.1016/0165-0173(86)90002-0)
58. Hodgkins P, Montejano L, Sasane R, Huse D. 2011 Cost of illness and comorbidities in adults diagnosed with attention-deficit/hyperactivity disorder: a retrospective analysis. Prim Care Companion CNS Disord. 13, pcc.10m01030. (doi:10.4088/PCC.10m01030)
59. Mehta MA, Goodyer IM, Sahakian BJ. 2004 Methylphenidate improves working memory and set-shifting in AD/HD: relationships to baseline memory capacity. J. Child Psychol. Psychiatry 45, 293-305. (doi:10.1111/j.1469-7610.2004.00221.x)
60. Kempton S, Vance A, Maruff P, Luk E, Costin J, Pantelis C. 1999 Executive function and attention deficit hyperactivity disorder: stimulant medication and better executive function performance in children. Psychol. Med. 29, 527-538. (doi:10.1017/S0033291799008338)
61. McLean A, Dowson J, Toone B, Young S, Bazanis E, Robbins TW, Sahakian BJ. 2004 Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder. Psychol. Med. 34, 681-692. (doi:10.1017/S0033291703001296)
62. Turner DC, Blackwell AD, Dowson JH, McLean A, Sahakian BJ. 2005 Neurocognitive effects of methylphenidate in adult attention-deficit/hyperactivity disorder. Psychopharmacology (Berl.) 178, 286-295. (doi:10.1007/s00213-004-1993-5)
63. Elliott R, Sahakian BJ, Matthews K, Bannerjea A, Rimmer J, Robbins TW. 1997 Effects of methylphenidate on spatial working memory and planning in healthy young adults. Psychopharmacology (Berl.) 131, 196-206. (doi:10.1007/s002130050284)
64. Mehta MA, Owen AM, Sahakian BJ, Mavaddat N, Pickard JD, Robbins TW. 2000 Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain. J. Neurosci. 20, RC65.
65. del Campo N et al. 2013 A positron emission tomography study of nigro-striatal dopaminergic mechanisms underlying attention: implications for ADHD and its treatment. Brain 136, 3252-3270. (doi:10.1093/brain/awt263)
66. DeVito EE, Blackwell AD, Clark L, Kent L, Dezsery AM, Turner DC, Aitken MR, Sahakian BJ. 2009 Methylphenidate improves response inhibition but not reflection-impulsivity in children with attention deficit hyperactivity disorder (ADHD). Psychopharmacology (Berl.) 202, 531-539. (doi:10.1007/s00213-008-1337-y)
67. Coghill DR, Seth S, Pedroso S, Usala T, Currie J, Gagliano A. 2014 Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis. Biol. Psychiatry 76, 603-615. (doi:10.1016/j.biopsych.2013.10.005)
68. Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ. 2004 Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder. Biol. Psychiatry 55, 1031-1040. (doi:10.1016/j.biopsych.2004.02.008)
69. Chamberlain SR, Del Campo N, Dowson J, Muller U, Clark L, Robbins TW, Sahakian BJ. 2007 Atomoxetine improved response inhibition in adults with attention deficit/hyperactivity disorder. Biol. Psychiatry 62, 977-984. (doi:10.1016/j.biopsych.2007.03.003)
70. Insel TR, Cuthbert BN, Garvey MJ, Heinssen R, Pine DS, Quinn K, Sanislow CA, Wang P. 2010 Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am. J. Psychiatry 167, 748-751. (doi:10.1176/appi.ajp.2010.09091379)
71. Scoriels L, Barnett JH, Soma PK, Sahakian BJ, Jones PB. 2012 Effects of modafinil on cognitive functions in first episode psychosis. Psychopharmacology (Berl.) 220, 249-258. (doi:10.1007/s00213-011-2472-4)
72. Green MF, Kern RS, Braff DL, Mintz J. 2000 Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the ‘right stuff’? Schizophr. Bull. 26, 119-136. (doi:10.1093/oxfordjournals.schbul.a033430)
73. Harvey PD, Bertisch H, Friedman JI, Marcus S, Parrella M, White L, Davis KL. 2003 The course of functional decline in geriatric patients with schizophrenia: cognitive-functional and clinical symptoms as determinants of change. Am. J. Geriatr. Psychiatry 11, 610-619. (doi:10.1097/00019442-200311000-00005)
74. Davidson M, Keefe RS. 1995 Cognitive impairment as a target for pharmacological treatment in schizophrenia. Schizophr. Res. 17, 123-129. (doi:10.1016/0920-9964(95)00037-M)
75. Martens L, Addington J. 2001 The psychological well-being of family members of individuals with schizophrenia. Soc. Psychiatry Psychiatr. Epidemiol. 36, 128-133. (doi:10.1007/s001270050301)
76. Sevy S, Davidson M. 1995 The cost of cognitive impairment in schizophrenia. Schizophr. Res. 17, 1-3. (doi:10.1016/0920-9964(95)00025-H)
77. Fineberg NA et al. 2013 The size, burden and cost of disorders of the brain in the UK. J. Psychopharmacol. 27, 761-770. (doi:10.1177/0269881113495118)
78. Barnett JH, Robbins TW, Leeson VC, Sahakian BJ, Joyce EM, Blackwell AD. 2010 Assessing cognitive function in clinical trials of schizophrenia. Neurosci. Biobehav. Rev. 34, 1161-1177. (doi:10.1016/j.neubiorev.2010.01.012)
79. Scoriels L, Barnett JH, Murray GK, Cherukuru S, Fielding M, Cheng F, Lennox BR, Sahakian BJ, Jones PB. 2011 Effects of modafinil on emotional processing in first episode psychosis. Biol. Psychiatry 69, 457-464. (doi:10.1016/j.biopsych.2010.09.043)
80. Turner DC, Clark L, Pomarol-Clotet E, McKenna P, Robbins TW, Sahakian BJ. 2004 Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology 29, 1363-1373. (doi:10.1038/sj.npp.1300457)
81. Farrow TF, Hunter MD, Haque R, Spence SA. 2006 Modafinil and unconstrained motor activity in schizophrenia: double-blind crossover placebocontrolled trial. Br. J. Psychiatry 189, 461-462. (doi:10.1192/bjp.bp.105.017335)
82. Rosenthal MH, Bryant SL. 2004 Benefits of adjunct modafinil in an open-label, pilot study in patients with schizophrenia. Clin. Neuropharmacol. 27, 38-43. (doi:10.1097/00002826-200401000-00011)
83. Hunter MD, Ganesan V, Wilkinson ID, Spence SA. 2006 Impact of modafinil on prefrontal executive function in schizophrenia. Am. J. Psychiatry 163, 2184-2186. (doi:10.1176/appi.ajp.163.12.2184)
84. Barch DM. 2010 Pharmacological strategies for enhancing cognition in schizophrenia. In Behavioral neurobiology of schizophrenia and its treatment (ed. NR Swerdlow), pp. 43-96. Berlin, Germany: Springer.
85. Sahakian B, Jones G, Levy R, Gray J, Warburton D. 1989 The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br. J. Psychiatry 154, 797-800. (doi:10.1192/bjp.154.6.797)
86. Insel TR, Sahakian BJ. 2012 Drug research: a plan for mental illness. Nature 483, 269. (doi:10.1038/483269a)
87. Insel TR et al. 2013 Innovative solutions to novel drug development in mental health. Neurosci. Biobehav. Rev. 37, 2438-2444. (doi:10.1016/j.neubiorev.2013.03.022)
88. Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P. 2011 A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am. J. Psychiatry 168, 472-485. (doi:10.1176/appi.ajp.2010.10060855)
89. McGurk SR, Twamley EW, Sitzer DI, McHugo GJ, Mueser KT. 2007 A meta-analysis of cognitive remediation in schizophrenia. Am. J. Psychiatry 164, 1791-1802. (doi:10.1176/appi.ajp.2007.07060906)
90. Bellucci DM, Glaberman K, Haslam N. 2003 Computer-assisted cognitive rehabilitation reduces negative symptoms in the severely mentally ill. Schizophr. Res. 59, 225-232. (doi:10.1016/S0920-9964(01)00402-9)
91. Subramaniam K, Luks TL, Fisher M, Simpson GV, Nagarajan S, Vinogradov S. 2012 Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia. Neuron 73, 842-853. (doi:10.1016/j.neuron.2011.12.024)
92. Sacks S, Fisher M, Garrett C, Alexander P, Holland C, Rose D, Hooker C, Vinogradov S. 2013 Combining computerized social cognitive training with neuroplasticity-based auditory training in schizophrenia. Clin. Schizophr. Relat. Psychoses 7, 78-86. (doi:10.3371/CSRP.SAFI.012513)
93. McGurk SR, Mueser KT, Pascaris A. 2005 Cognitive training and supported employment for persons with severe mental illness: one-year results from a randomized controlled trial. Schizophr. Bull. 31, 898-909. (doi:10.1093/schbul/sbi037)
94. McGurk SR, Mueser KT, Feldman K, Wolfe R, Pascaris A. 2007 Cognitive training for supported employment: 2-3 year outcomes of a randomized controlled trial. Am. J. Psychiatry 164, 437-441. (doi:10.1176/ajp.2007.164.3.437)
95. Cavallaro R et al. 2009 Computer-aided neurocognitive remediation as an enhancing strategy for schizophrenia rehabilitation. Psychiatry Res. 169, 191-196. (doi:10.1016/j.psychres.2008.06.027)
96. Kluwe-Schiavon B, Sanvicente-Vieira B, Kristensen CH, Grassi-Oliveira R. 2013 Executive functions rehabilitation for schizophrenia: a critical systematic review. J. Psychiatr. Res. 47, 91-104. (doi:10.1016/j.jpsychires.2012.10.001)
97. Barnett JH, Sahakian BJ, Werners U, Hill KE, Brazil R, Gallagher O, Bullmore ET, Jones PB. 2005 Visuospatial learning and executive function are independently impaired in first-episode psychosis. Psychol. Med. 35, 1031-1041. (doi:10.1017/S0033291704004301)
98. Sahakian BJ. 2011 Benefits and opportunities. In Brain waves module 1: neuroscience, society and policy (ed. The Royal Society), pp. 61-68. London, UK: Royal Society.
99. Sahakian BJ, Malloch G, Kennard C. 2010 A UK strategy for mental health and wellbeing. Lancet 375, 1854-1855. (doi:10.1016/S0140-6736(10)60817-3)
100. Hayden EC. 2012 Treating schizophrenia: game on. Nature 483, 24-26. (doi:10.1038/483024a)
101. Fisher M, Holland C, Subramaniam K, Vinogradov S. 2010 Neuroplasticity-based cognitive training in schizophrenia: an interim report on the effects 6 months later. Schizophr. Bull. 36, 869-879. (doi:10.1093/schbul/sbn170)
102. Saleem MM, Harte MK, Marshall KM, Scally A, Brewin A, Neill JC. 2013 Positive effects of a novel cognitive remediation computer game (X-Cog) in first episode psychosis: a pilot study. Psychosis 6, 215-219. (doi:10.1080/17522439.2013.791876)
103. Kuhn S, Gleich T, Lorenz RC, Lindenberger U, Gallinat J. 2014 Playing Super Mario induces structural brain plasticity: gray matter changes resulting from training with a commercial video game. Mol. Psychiatry 19, 265-271. (doi:10.1038/mp.2013.120)
104. First MB, Spitzer RL, Gibbon M, Williams JBW. 2002 Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition. (SCID-I/P). New York, NY: Biometrics Research.
105. American Psychiatric Association. 2013 Diagnostic and statistical manual of mental disorders, Fifth edition (DSM-5), p. 991. Washington, DC: American Psychiatric Association.
106. Nelson HE. 1982 National adult reading test (NART): test manual. Windsor, UK: NFER-Nelson.
107. Overall JE, Gorham DR. 1962 The brief psychiatric rating scale. Psychol. Rep. 10, 799-812. (doi:10.2466/pr0.1962.10.3.799)
108. Endicott J, Spitzer RL, Fleiss JL, Cohen J. 1976 The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch. Gen. Psychiatry 33, 766-771. (doi:10.1001/archpsyc.1976.01770060086012)
109. Nicholson IR, Chapman JE, Neufeld RWJ. 1995 Variability in BPRS definitions of positive and negative symptoms. Schizophr. Res. 17, 177-185. (doi:10.1016/0920-9964(94)00088-P)
110. Smith ME, Farah MJ. 2011 Are prescription stimulants ‘smart pills’? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals. Psychol. Bull. 137, 717-741. (doi:10.1037/a0023825)
111. Repantis D, Schlattmann P, Laisney O, Heuser I. 2010 Modafinil and methylphenidate for neuroenhancement in healthy individuals: a systematic review. Pharmacol. Res. 62, 187-206. (doi:10.1016/j.phrs.2010.04.002)
112. Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ. 2003 Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology (Berl.) 165, 260-269. (doi:10.1007/s00213-002-1250-8)
113. Muller U, Rowe JB, Rittman T, Lewis C, Robbins TW, Sahakian BJ. 2013 Effects of modafinil on nonverbal cognition, task enjoyment and creative thinking in healthy volunteers. Neuropharmacology 64, 490-495. (doi:10.1016/j.neuropharm.2012.07.009)
114. Sugden C, Housden CR, Aggarwal R, Sahakian BJ, Darzi A. 2011 Effect of pharmacological enhancement on the cognitive and clinical psychomotor performance of sleep-deprived doctors: a randomized controlled trial. Ann. Surg. 255, 222-227. (doi:10.1097/SLA.0b013e3182306c99)
115. Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. 2003 Effects of caffeine on human health. Food Addit. Contam. 20, 1-30. (doi:10.1080/0265203021000007840)
116. Chamberlain SR, Müller U, Blackwell AD, Clark L, Robbins TW, Sahakian BJ. 2006 Neurochemical modulation of response inhibition and probabilisticlearning in humans. Science 311, 861-863. (doi:10.1126/science.1121218)
117. Graf H, Abler B, Freudenmann R, Beschoner P, Schaeffeler E, Spitzer M, Schwab M, Grön G. 2011 Neural correlates of error monitoring modulated by atomoxetine in healthy volunteers. Biol. Psychiatry 69, 890-897. (doi:10.1016/j.biopsych.2010.10.018)
118. Kuo MF, Paulus W, Nitsche MA. 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)
119. Demirtas-Tatlidede A, Vahabzadeh-Hagh AM, Pascual-Leone A. 2013 Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders? Neuropharmacology 64, 566-578. (doi:10.1016/j.neuropharm.2012.06.020)
120. Padberg F, Zwanzger P, Thoma H, Kathmann N, Haag C, Greenberg B, Hampel H, Möller H-J. 1999 Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. Psychiatry Res. 88, 163-171. (doi:10.1016/S0165-1781(99)00092-X)
121. Hausmann A et al. 2004 No deterioration of cognitive performance in an aggressive unilateral and bilateral antidepressant rTMS add-on trial. J. Clin. Psychiatry 65, 772-782. (doi:10.4088/JCP.v65n0608)
122. Moser DJ, Jorge RE, Manes F, Paradiso S, Benjamin ML, Robinson RG. 2002 Improved executive functioning following repetitive transcranial magnetic stimulation. Neurology 58, 1288-1290. (doi:10.1212/WNL.58.8.1288)
123. Höppner J, Schulz M, Irmisch G, Mau R, Schläfke D, Richter J. 2003 Antidepressant efficacy of two different rTMS procedures: high frequency over left versus low frequency over right prefrontal cortex compared with sham stimulation. Eur. Arch. Psychiatry Clin. Neurosci. 253, 103-109. (doi:10.1007/s00406-003-0416-7)
124. Mogg A, Purvis R, Eranti S, Contell F, Taylor JP, Nicholson T, Brown RG, McLoughlin DM. 2007 Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: a randomized controlled pilot study. Schizophr. Res. 93, 221-228. (doi:10.1016/j.schres.2007.03.016)
125. Slotema CW, Blom JD, Hoek HW, Sommer IE. 2010 Should we expand the toolbox of psychiatric treatment methods to include repetitive transcranial magnetic stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J. Clin. Psychiatry 71, 873-884. (doi:10.4088/JCP.08m04872gre)
126. Rossi S, Hallett M, Rossini PM, Pascual-Leone A. 2009 Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin. Neurophysiol. 120, 2008-2039. (doi:10.1016/j.clinph.2009.08.016)
127. Schonfeldt-Lecuona C, Cardenas-Morales L, Moreno-Aguirre A, Dorn K, Langguth B, Bruhl AB, Kammer T, Herwig U. 2012 Effect of 1 Hz repetitive transcranial magnetic stimulation over the auditory cortex on audiometry and otoacustic emissions. Brain Topogr. 25, 241-247. (doi:10.1007/s10548-012-0218-1)
128. Shiozawa P, Fregni F, Bensen˜or IM, Lotufo PA, Berlim MT, Daskalakis JZ, Cordeiro Q, Brunoni AR. 2014 Transcranial direct current stimulation for major depression: an updated systematic review and meta-analysis. Int. J. Neuropsychol. 17, 1443-1452. (doi:10.1017/S1461145714000418)
129. Kalu UG, Sexton CE, Loo CK, Ebmeier KP. 2012 Transcranial direct current stimulation in the treatment of major depression: a meta-analysis. Psychol. Med. 42, 1791-1800. (doi:10.1017/S0033291711003059)
130. Schretlen DJ, van Steenburgh JJ, Varvaris M, Vannorsdall TD, Andrejczuk MA, Gordon B. In press. Can transcranial direct current stimulation improve cognitive functioning in adults with schizophrenia? Clin. Schizophr. Relat. Psychoses 1-27. (doi:10.3371/CSRP.SCST.103114)
131. Coffman BA, Clark VP, Parasuraman R. 2014 Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation. Neuroimage 85, 895-908. (doi:10.1016/j.neuroimage.2013.07.083)
132. Brunoni AR, Vanderhasselt M-A. 2014 Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis. Brain Cogn. 86, 1-9. (doi:10.1016/j.bandc.2014.01.008)
133. McIntire LK, McKinley RA, Goodyear C, Nelson J. 2014 A comparison of the effects of transcranial direct current stimulation and caffeine on vigilance and cognitive performance during extended wakefulness. Brain Stimul. 7, 499-507. (doi:10.1016/j.brs.2014.04.008)
134. Horvath JC, Carter O, Forte JD. 2014 Transcranial direct current stimulation: five important issues we aren’t discussing (but probably should be). Front. Syst. Neurosci. 8, 2. (doi:10.3389/fnsys.2014.00002)
135. Davis NJ. 2014 Transcranial stimulation of the developing brain: a plea for extreme caution. Front. Hum. Neurosci. 8, 600. (10.3389/fnhum.2014.00600)
136. Bikson M, Bestmann S, Edwards D. 2013 Neuroscience: transcranial devices are not playthings. Nature 501, 167. (doi:10.1038/501167b)
137. Giedd JN, Raznahan A, Alexander-Bloch A, Schmitt E, Gogtay N, Rapoport JL. 2015 Child psychiatry branch of the national institute of mental health longitudinal structural magnetic resonance imaging study of human brain development. Neuropsychopharmacology 40, 43-49. (doi:10.1038/npp.2014.236)
138. Singh I, Bard I, Jackson J. 2014 Robust resilience and substantial interest: a survey of pharmacological cognitive enhancement among university students in the UK and Ireland. PLoS ONE 9, e105969. (doi:10.1371/journal.pone.0105969)
139. Webb JR, Valasek MA, North CS. 2013 Prevalence of stimulant use in a sample of US medical students. Ann. Clin. Psychiatry 25, 27-32.
140. Emanuel RM, Frellsen SL, Kashima KJ, Sanguino SM, Sierles FS, Lazarus CJ. 2013 Cognitive enhancement drug use among future physicians: findings from a multi-institutional census of medical students. J. Gen. Intern. Med. 28, 1028-1034. (doi:10.1007/s11606-012-2249-4)
141. Dietz P, Striegel H, Franke AG, Lieb K, Simon P, Ulrich R. 2013 Randomized response estimates for the 12-month prevalence of cognitive-enhancing drug use in university students. Pharmacotherapy 33, 44-50. (doi:10.1002/phar.1166)
142. Maier LJ, Liechti ME, Herzig F, Schaub MP. 2013 To dope or not to dope: neuroenhancement with prescription drugs and drugs of abuse among Swiss university students. PLoS ONE 8, e77967. (doi:10.1371/journal.pone.0077967)
143. Low KG, Gendaszek AE. 2002 Illicit use of psychostimulants among college students: a preliminary study. Psychol. Health Med. 7, 283-287. (doi:10.1080/13548500220139386)
144. Normann C, Berger M. 2008 Neuroenhancement: status quo and perspectives. Eur. Arch. Psychiatry Clin. Neurosci. 258(Suppl. 5), 110-114. (doi:10.1007/s00406-008-5022-2)
145. Vastag B. 2004 Poised to challenge need for sleep, ‘wakefulness enhancer’ rouses concerns. JAMA 291, 167-170. (doi:10.1001/jama.291.2.167)
146. Academy of Medical Sciences. 2008 Brain Science, Addiction and Drugs (ed. Academy of Medical Sciences). London, UK: The Academy of Medical Sciences.
147. Duke University. 2014 Policy on academic dishonesty. See http://studentaffairs.duke.edu/conduct/z-policies/academic-dishonesty (15.12.2014).
148. Sahakian BJ, Morein-Zamir S. 2009 Neuroscientists need neuroethics teaching. Science 325, 147. (doi:10.1126/science.325_147a)
149. Sahakian BJ, Morein-Zamir S. 2011 Neuroethical issues in cognitive enhancement. J. Psychopharmacol. 25, 197-204. (doi:10.1177/0269881109106926)
150. Hyman Steven E. 2011 Cognitive enhancement: promises and perils. Neuron 69, 595-598. (doi:10.1016/j.neuron.2011.02.012)
151. Santoni de Sio F, Faulmüller N, Vincent NA. 2014 How cognitive enhancement can change our duties. Front. Syst. Neurosci. 8, 131. (doi:10.3389/fnsys.2014.00131)
152. Academy of Medical Sciences. 2012 Human enhancement and the future of work. Report from a joint workshop hosted by the Academy of Medical Sciences, the British Academy, the Royal Academy of Engineering and the Royal Society (ed. Academy of Medical Sciences). London, UK: The Academy of Medical Sciences. See https://royalsociety.org/~/media/policy/projects/human-enhancement/2012-11-06-human-enhancement.pdf (15.12.2014).