Dopaminergic deficiency syndrome in the picture of severe brain injury in the presence of protracted depression of consciousness

Objective: to determine the clinical and electroencephalographic (EEG) signs of dopaminergic deficiency (DD) when recovering consciousness in patients with severe brain injury (SBI).

Patients and methods. Thirty-five patients (23 men and 12 women; mean age 29±13 years), who had experienced SBI accompanied by coma (mean duration 17±6 days) and treated at the Acad. N.N. Burdenko Research Institute of Neurosurgery, were examined. The comprehensive examination included neurological and mental status evaluation and EEG with dynamic assessment of the pattern.

Results and discussion. The authors defined a constellation of neurological symptoms as increased extrapyramidal muscle tone, resting tremor, and specific autonomic dysfunction, which was characteristic of autonomic status and some forms of mutism, and, in accordance with the data available in the literature, was defined as DD syndrome. The latter accompanied by characteristic EEG changes: its pattern’s higher synchronized β-activity (13–14 Hz) enhanced in the frontal and anterior temporal regions. The administration of amantadine sulfate was followed by an increase (even as compared with the normal value) in the dynamics of the power of mainly of β3 (at frequencies of 17–23 Hz) and θ2 (5.9–7.4 Hz) bands along the anterior regions more frequently on the right; by the amplification of intrahemispheric connections (in the occipitotemporal regions) in the β3 band (more often on the right) and θ one (5.9–7.4 Hz) in the right occipitotemporal region. The agent had no significant effect on the SBI outcome assessed 12 months after injury, but it affected the clinical symptoms of DD.

1. Потапов АА, Лихтерман ЛБ, Кравчук АД, Рошаль ЛМ. Черепно-мозговая травма: проблемы и перспективы. Вопросы нейрохирургии им. Н.Н. Бурденко. 2009;(2):3–8. [Potapov AA, Likhterman LB, Kravchuk AD, Roshal' LM. Traumatic brain injury: problems and perspectives. Voprosy neirokhirurgii im. N.N. Burdenko. 2009;(2):3–8. (In Russ.)]

2. Bales JW, Wagner AK, Kline AE, Dixon CE. Persistent cognitive dysfunction after traumatic brain injury: a dopamine hypothesis. Neurosci Biobehav Rev. 2009;33:981–1003. DOI: http://dx.doi.org/10.1016/j.neubiorev. 2009.03.011.

3. Зайцев ОС, Потапов АА, Шарова ЕВ и др. Комплексная реабилитация пострадавших с психическими расстройствами вследствие тяжелой черепно-мозговой травмы. Неврологический вестник. Журнал им. В.М. Бехтерева. 2009;XLI(4):18–21. [Zaitsev OS, Potapov AA, Sharova EV. Complex rehabilitation of patients with mental disorders after severe cranio-cerebral traumas. Nevrologicheskii vestnik. Zhurnal im. V.M. Bekhtereva. 2009;XLI(4):18–21. (In Russ.)]

4. Смирнов ЛИ. Патологическая анатомия и патогенез травматических заболеваний нервной системы. Том 1–2. Москва: Издательство АМН СССР. 1947–1949. С. 310. [Smirnov LI. Patologicheskaya anatomiya i patogenez travmaticheskikh zabolevanii nervnoi sistemy [Pathological anatomy and pathogenesis of traumatic diseases of nervous system]. Vol. 1–2. Moscow: Izdatel'stvo AMN SSSR. 1947–1949. P. 310.]

5. Кондратьев АН, Ивченко ИМ. Анестезия и интенсивная терапия травмы ЦНС. Санкт-Петербург: Санкт-Петербургское медицинское издательство; 2002. С. 128. [Kondrat'ev AN, Ivchenko IM. Anesteziya i intensivnaya terapiya travmy TsNS [Anesthesia and intensive therapy of a trauma of TsNS]. St-Petersburg: Sankt-Peterburgskoe meditsinskoe izdatel'stvo; 2002. P. 128.]

6. Reilly PL, Bullock R, editors. Head Injury, pathophysiology and management. 2nd ed. 2005. P. 501–5. DOI: http://dx.doi.org/10.1201/b13492.

7. Seeman P, Tedesco JL, Lee T, et al. Dopamine receptors in the central nervous system. Fed Proc. 1978;37:131–6.

8. Chudasama Y, Robbins TW. Functions of frontostriatal systems in cognition: comparative neuropsychopharmacological studies in rats, monkeys and deficits induced by closed-head injury in the mouse. J Neurotrauma. 2006;15:231–7.

9. Chen Y, Shohami E, Constantini S, Weinstock M. Rivastigmine, a brain-selective acetylcholinesterase inhibitor, ameliorates cognitive and motor deficits induced by closedhead injury in the mouse. J Neurotrauma. 1998;15(4):231–7. DOI: http://dx.doi.org/ 10.1089/neu.1998.15.231.

10. Noble JM, Hauser WA, Silver JM. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology. 2007;68:1749–50. DOI: http://dx.doi.org/10.1212/01.wnl.0000266745.86958.ce.

11. Tenovuo O. Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury-clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiat. 2005;29:61–7. DOI: http://dx.doi.org/10.1016/j.pnpbp.2004.10.006.

12. Raz A. Anatomy of attentional networks. J Anat Rec B New Anat. 2004;281:21–36. DOI: http://dx.doi.org/10.1002/ar.b.20035.

13. Ding Y, Yao B, Lai Q, McAllister JP. Impaired motor learning and diffuse axonal damage in motor and visual systems of the rat following traumatic brain injury. J Neurol Res. 2001;23:193–202. DOI: http://dx.doi.org/10.1179/016164101101198334.

14. Dunn-Meynell AA, Levin BE. Histological markers of neuronal, axonal and astrocytic changes after lateral rigid impact traumatic brain injury. J Brain Res. 1997;761:25–41. DOI: http://dx.doi.org/10.1016/S0006-8993(97)00210-2.

15. Dietrich WD, Alonso O, Halley M. Early microvascular and neuronal consequences of traumatic brain injury: a light and electron microscopic study in rats. J Neurotrauma. 1994;11:289–301. DOI: http://dx.doi.org/10.1089/neu.1994.11.289.

16. Fontaine A, Azouvi P, Remy P, et al. Functional anatomy of neuropsychological deficits after severe traumatic brain injury. Neurology. 1999;53:1963–8. DOI: http://dx.doi.org/10.1212/WNL.53.9.1963.

17. Hicks RR, Smith DH, Lowenstein DH, et al. Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus. J Neurotrauma. 1993;10:405–14. DOI: http://dx.doi.org/10.1089/neu.1993.10.405.

18. Smith DH, Lowenstein DH, Gennarelli TA, McIntosh TK. Persistent memory dysfunction is associated with bilateral hippocampal damage following experimental brain injury. Neurosci Lett. 1994;168:151–4. DOI: http://dx.doi.org/10.1016/0304-3940(94)90438-3.

19. Lemon N, Manahan-Vaughan D. Dopamine D1/D5 receptors gate the acquisition of novel information through hippocampal long-term potentiation and long-term depres-sion. J Neurosci. 2006;26:7723–9. DOI: http://dx.doi.org/10.1523/JNEUROSCI. 1454-06.2006.

20. Dixon CE, Lyeth BG, Povlishock JT, et al. A fluid percussion model of experimental brain injury in the rat. J Neurosurg. 1987;67:110–9. DOI: http://dx.doi.org/10.3171/jns.1987.67. 1.011021.

21. Lighthall JW, Dixon CE, Anderson TE. Experimental models of brain injury. J Neurotrauma. 1989;6:83–97. DOI: http://dx.doi.org/10.1089/neu.1989.6.83.

22. Угрюмов ВМ, редактор. Тяжелая закрытая травма черепа и головного мозга. Москва: Медицина; 1976. С. 303–7. [Ugryumov VM, editor. Tyazhelaya zakrytaya travma cherepa i golovnogo mozga [The severe closed injury of a skull and brain]. Moscow: Meditsina; 1976. P. 303–7.]

23. Goldstein LB. Neuropharmacology of TBIinduced plasticity. J Brain Inj. 2003;17:685–94. DOI: http://dx.doi.org/10.1080/0269905031000107179.

24. McAllister TW, Flashman LA, Sparling MB, Saykin AJ. Working memory deficits after traumatic brain injury: catecholaminergic mechanisms and prospects for treatment – a review. J Brain Inj. 2004;18:331–50. DOI: http://dx.doi.org/10.1080/026990503 10001617370.

25. Gentilini M, Barbieri C, De Renzi E, Faglioni P. Space exploration with and without the aid of vision in hemisphere-damaged patients. J Cortex. 1989;25: 643–51. DOI: http://dx.doi.org/10.1016/S0010-9452(89)80024-3.

26. Draper K, Ponsford J. Cognitive functioning ten years following traumatic brain injury and rehabilitation. Neuropsychology. 2008;22:618–25. DOI: http://dx.doi.org/10.1037/0894- 4105.22.5.618.

27. Ponsford J, Kinsella G. Attentional deficits following closed-head injury. J Clin Exp Neuropsychol. 1992;14:822–38. DOI: http://dx.doi.org/10.1080/01688639208402865.

28. McDowell S, Whyte J, D'Esposito M. Working memory impairments in traumatic brain injury: evidence from a dual-task paradigm. Neuropsychologia. 1997;35:1341–53. DOI: http://dx.doi.org/10.1016/S0028-3932(97)00082-1.

29. Wise SP, Murray EA, Gerfen CR. The frontal cortex-basal ganglia system in primates. Crit Rev Neurobiol. 1996;10:317–56. DOI: http://dx.doi.org/10.1615/CritRev Neurobiol.v10.i3-4.30.

30. Brennan AR, Arnsten AF. Neuronal mechanisms underlying attention deficit hyperactivity disorder: the influence of arousal on prefrontal cortical function. J Ann NY Acad Sci. 2008;1129:236–45. DOI: http://dx.doi.org/10.1196/annals.1417.00731.

31. Sanders MJ, Sick TJ, Perez-Pinzon MA, et al. Chronic failure in the maintenance of longterm potentiation following fluid percussion injury in the rat. J Brain Res. 2000;861:79–86. DOI: http://dx.doi.org/10.1016/S0006-8993(00)01986-7.

32. Baddeley A. Working memory. J Science. 1992;255:556–9. DOI: http://dx.doi.org/10.1126/science.1736359.

33. Bales JW, Wagner AK, Kline AE, Dixon CE. Persistent cognitive dysfunction after traumatic brain injury: a dopamine hypothesis. Neurosci Biobehav Rev. 2009;33:981–1003. DOI: http://dx.doi.org/10.1016/j.neubiorev.2009.03.011.

34. Oddy M, Coughlan T, Tyerman A, Jenkins D. Social adjustment after closed head injury: a further follow-up seven years after injury. J Neurol Neurosurg Psychiatry. 1985;48:564–8. DOI: http://dx.doi.org/10.1136/jnnp.48.6.564.

35. Arciniegas DB, Topkoff J, Silver JM. Neuropsychiatric aspects of traumatic brain injury. Curr Treat Options Neurol. 2000;2(2):169–86. DOI: http://dx.doi.org/10. 1007/s11940-000-0017-y.

36. Moldover JE, Goldberg KB, Prout MF. Depression after traumatic brain injury: a review of evidence for clinical heterogeneity. J Neuropsychol. 2004;14:143–54. DOI:

37. Mega MS, Cummings JL. Frontal-subcortical circuits and neuropsychiatric disorders. J Neuropsychiatry Clin Neurosci. 1994;6:358–70.

38. Donnemiller E, Brenneis C, Wissel J, et al. Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPECT study using 123I-beta-CIT and 123I-IBZM. Eur J Nucl Med. 2000;27:1410–4. DOI: http://dx.doi.org/10.1007/s002590000308.

39. Meythaler JM, Brunner RC, Johnson A, Novack TA. Amantadine to improve neurorecovery in traumatic brain injury-associated diffuse axonal injury: a pilot double-blind randomized trial. J Head Trauma Rehabil. 2002;17:300–13. DOI: http://dx.doi.org/10.1097/00001199- 200208000-00004.

40. Бархатова ВП. Нейротрансмиттерная организация базальных ганглиев. В кн.: Экстрапирамидные расстройства. Руководство по диагностике и лечению. Под ред. В.Н. Штока, И.А. Ивановой-Смоленской, О.С. Левина. Москва: МЕДпресс-информ; 2002. С. 9–15. [Barkhatova VP. Neyrotransmitter organization of bazal ganglies. In: Ekstrapiramidnye rasstroistva. Rukovodstvo po diagnostike i lecheniyu [Extrapyramidal frustration. Guide to diagnostics and treatment]. Shtok VN, Ivanova-Smolenskaya IA, Levin OS, editors. Moscow: MEDpress-inform; 2002. P. 9–15.]

41. Голубев ВЛ, Левин ЯИ, Вейн AM. Болезнь Паркинсона и синдром паркинсонизма. Москва: МЕДпресс-информ; 2000. С. 416. [Golubev VL, Levin YaI, Vein AM. Bolezn' Parkinsona i sindrom parkinsonizma [Parkinson's disease and syndrome of parkinsonism]. Moscow: MEDpress-inform; 2000. P. 416.]

42. Wagle AC, Wagle SA, Markova IS, Berrios GE. Psychiatric Morbidity in Huntington's disease. Neurology, Psychiatry and Brain Research. 2000;8:5–16.

43. Луцкий ИС, Евтушенко СК, Симонян ВА. Болезнь Паркинсона (клиника, диагностика, принципы терапии). Международный неврологический журнал. 2011;5(43):159–74. [Lutskii IS, Evtushenko SK, Simonyan VA. Parkinson's disease (clinic, diagnostics, principles of therapy). Mezhdunarodnyi nevrologicheskii zhurnal. 2011;5(43):159–74. (In Russ.)]

44. Аракелян РК, Неробкова ЕА, Катунина ЕА. Функциональная активность головного мозга у пациента с болезнью Паркинсона при лечении сульфатом амантадина. Журнал неврологии и психиатрии им. С.С. Корсакова. 2005;105(9):18–22. [Arakelyan RK, Nerobkova EA, Katunina EA. Funktsional'naya aktivnost' golovnogo mozga u patsienta s bolezn'yu Parkinsona pri lechenii sul'fatom amantadina. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2005;105(9):18–22. (In Russ.)]

45. Soikkeli R, Partanen J, Soininen H, et al. Slowing of EEG in Parkinson's disease. Electroencephalogr Clin Neurophysiol. 1991;79(3):159–65. DOI: http://dx.doi.org/10.1016/0013-4694(91)90134-P.

46. Fonseca LC, Tedrus GM, Letro GH, Bossoni AS. Dementia, mild cognitive impairment and quantitative EEG in patients with Parkinson's disease. J Clin EEG Neurosci. 2009;40(3):168–72. DOI: http://dx.doi.org/10.1177/155005940904000309.

47. Обухов ЮВ, Королев МС, Карабанов АВ и др. Особенности частотно-временной структуры ЭЭГ у пациентов на ранних стадиях болезни Паркинсона. Технологии живых систем. 2011;8:40–7. [Obukhov YuV, Korolev MS, Karabanov AV, et al. The peculiarities of EEG time-frequency structure in patients of early stage of Parkinson disease. Tekhnologii zhivykh sistem. 2011;8:40–7. (In Russ.)]

48. Arciniegas DB. The cholinergic hypothesis of cognitive impairment caused by traumatic brain injury. Curr Psychiatry Rep. 2003;5:391–9. DOI: http://dx.doi.org/10.1007/s11920-003- 0074-5.

49. Челяпина МВ, Шарова ЕВ, Зайцев ОС. Клинические и электроэнцефалографические эффекты сульфата амантадина (ПК-Мерц) на фоне угнетенного сознания вследствие тяжелой травмы головного мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. 2011;111(5):24–9. [Chelyapina MV, Sharova EV, Zaitsev OS. Clinical and electroencephalographic effects of amantadine sulfate (PK-Merz) on consciousness disorders due to the severe traumatic brain injury. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011;111(5):24–9. (In Russ.)]

50. Доброхотова ТА, Гриндель ОМ, Брагина НН и др. Восстановление сознания после длительной комы у больных с тяжелой черепно-мозговой травмой. Журнал невропатологии и психиатрии им. C.C. Корсакова. 1985;85(5):720–6. [Dobrokhotova TA, Grindel' OM, Bragina NN, et al. Restoration of consciousness after a long coma at patients with a severe craniocereberal injury. Zhurnal nevropatologii i sikhiatrii im. S.S. Korsakova. 1985;85(5):720–6. (In Russ.)]

51. Доброхотова ТА, Потапов АА, Зайцев ОС, Лихтерман ЛБ. Обратимые посткоматозные бессознательные состояния. Социальная и клиническая психиатрия. 1996;6(2):26–36. [Dobrokhotova TA, Potapov AA, Zaitsev OS, Likhterman LB. Reversible post-coma unconsciousnesses. Sotsial'naya i klinicheskaya psikhiatriya. 1996;6(2):26–36. (In Russ.)]

52. Зайцев ОС. Проблемы восстановления психической деятельности после тяжелой черепно-мозговой травмы. Перший з’iзд нейрохiрургiв Украiни. Тези доповiдей. Киiв; 1993. С. 212. [Zaitsev OS. Problems of restoration of mental activity after a severe craniocereberal injury. Перший з’iзд нейрохiрургiв Украiни. Тези доповiдей. Киiв; 1993. P. 212.]

53. Fahn S, Marsden C, Calne D, et al., editors. Unified Parkinson's disease rating scale. Recent developments in Parkinson's disease. McMillan Healthcare Information. 1987;5:153–63.

54. McPeak LA Physiatric history and examination. In: Physical medicine and rehabilitation. Braddom R, editor. W.B. Saunders Company; 1996. P. 3–42.

55. Вейс М, Зембатый А. Физиотерапия. Москва: Медицина; 1986. 495 с. [Veis M, Zembatyi A. Fizioterapiya [Phisiotheraphi]. Moscow: Meditsina; 1986. 495 p.]

56. Коршунов AM. Особенности течения и эффективность лечения болезни Паркинсона. Дисc. докт. мед. наук. Москва; 2002. 304 с. [Korshunov AM. Osobennosti techeniya i effektivnost' lecheniya bolezni Parkinsona. Diss. dokt. med. nauk [Features of a current and efficiency of treatment of a Parkinson’s disease: Dr. Diss. (Med. Sci.)]. Moscow; 2002. 304 p.]

57. Teasdale JD, Fogarty SJ. Differential effects of induced mood on retrieval of pleasant and unpleasant events from episodic memory. J Abnorm Psychol. 1979;88:248–57.

58. Русинов ВС, Гриндель ОМ, Болдырева ГН, акар ЕМ. Биопотенциалы мозга человека. Математический анализ. Москва: Медицина; 1987. С. 254. [Rusinov VS, Grindel' OM, Boldyreva GN, Vakar EM. Biopotentsialy mozga cheloveka. Matematicheskii analiz [Biopotentials of a brain of the person. Mathematical analysis]. Moscow: Meditsina; 1987. P. 254.]

59. Коптелов ЮМ, Гнездицкий ВВ. Анализ скальповых потенциальных полей и трехмерная локализация эквивалентных источников эпилептической активности мозга человека. Журнал невропатологии и психиатрии им. С.С. Корсакова. 1989;89(6):11. [Koptelov YuM, Gnezditskii VV. Analysis of skalp potential fields and three-dimensional localization of equivalent sources of epileptic activity of a brain of the person. Zhurnal nevropatologii i psikhiatrii im. S.S. Korsakova. 1989;89(6):11. (In Russ.)]

60. Gambarelli Y, Gurinel G, Cherrot L, Mattei M. Computerized axial Tomography (an anat. atlas of sections of the Human body. Anatomy-Radiology-Scannes). Berlin: Heidelbetg N.Y.; 1977.

61. Гриндель ОМ, Машеров ЕЛ, Воронов ВГ. Методы математического анализа ЭЭГ. Нейрофизиологические исследования в клинике. Москва: Антидор. 2001. С. 24–38. [Grindel' OM, Masherov EL, Voronov VG. Metody matematicheskogo analiza EEG. Neirofiziologicheskie issledovaniya v klinike [Methods of the mathematical analysis of EEG. Neurophysiological researches in clinic]. Moscow: Antidor. 2001. P. 24–38.]

62. Воронов ВГ, Щекутьев ГА, Гриндель ОМ. Пакет программ для статистического сравнения записей ЭЭГ. Материалы международной конференции «Клинические нейронауки: нейроизиология неврология, нейрохирургия», Украина, Крым, Гурзуф, июнь 2003. С. 22–24. [Voronov VG, Shchekut'ev GA, Grindel' OM. The software package for statistical comparison of records EEG. Materialy mezhdunarodnoi konferentsii «Klinicheskie neironauki: neiro-fiziologiya nevrologiya, neirokhirurgiya», Ukraina, Krym, Gurzuf, iyun' 2003 [Materials of the international conference «Clinical neurosciences: neurophysiology neurology, neurosurgery», Ukraine, Crimea, Gurzuf, June. 2003]. P. 22–24.]

63. Dimpfel W. Pharmacological modulation of dopaminergic brain activity and its reflection in spectral frequencies of the rat electropharmacogram. Neuropsychobiology. 2008;58(3–4):178–86. DOI: http://dx.doi.org/10.1159/000191124.

64. Babiloni C, De Pandis MF, Vecchio F, et al. Cortical sources of resting state electroencephalographic rhythms in Parkinson's disease related dementia and Alzheimer's disease. J Clin Neurophysiol. 2011;122(12):2355–64. DOI: http://dx.doi.org/10.1016/j.clinph.2011. 03.029.

65. Ploeger GE, Spruijt BM, Cools AR. Spatial localization in the Morris water maze in rats: acquisition is affected by intra-accumbens injections of the dopaminergic antagonist haloperidol. J Behav Neurosci. 1994;108:927–34. DOI: http://dx.doi.org/10.1037/0735-7044.108.5.927.

66. Ploeger GE, Willemen AP, Cools AR. Role of the nucleus accumbens in social memory in rats. J Brain Res Bull. 1991;26:23–7. DOI: http://dx.doi.org/10.1016/0361-9230(91)90187-O.

67. Cools AR, Ellenbroek B, Heeren D, Lubbers L. Use of high and low responders to novelty in rat studies on the role of the ventral striatum in radial maze performance: effects of intra-accumbens injections of sulpiride. Can J Physiol Pharmacol. 1993 May–Jun;71(5–6):335–42. DOI: http://dx.doi.org/10.1139/y93-052.

68. Setlow B, McGaugh JL. Sulpiride infused into the nucleus accumbens posttraining impairs memory of spatial water maze training. J Behav Neurosci. 1998;112:603–10. DOI: http://dx.doi.org/10.1037/0735-7044.112.3.603.

69. Coccurello R, Adriani W, Oliverio A, Mele A. Effect of intra accumbens dopamine receptor agents on reactivity to spatial and non-spatial changes in mice. Psychopharmacology. 2000;152:189–99. DOI: http://dx.doi.org/10.1007/s002130000515.

70. Mitchell JB, Gratton A. Involvement of mesolimbic dopamine neurons in sexual behaviors: implications for the neurobiology of motivation. J Rev Neurosci. 1994;5:317–29.

71. Saatman KE, Duhaime AC, Bullock R. Classification of traumatic brain injury for targeted therapies. J Neurotrauma. 2008;25(7):719–38. DOI: http://dx.doi.org/10.1089/neu.2008.0586.

72. Baldo BA, Kelley AE. Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding. Psychopharmacology. 2007;191:439–59. DOI: http://dx.doi.org/10.1007/s00213-007-0741-z.

73. Wickens JR, Budd CS, Hyland BI, Arbuthnott GW. Striatal contributions to reward and decision making: making sense of regional variations in a reiterated processing matrix. Ann NY Acad Sci. 2007;1104:192–212. DOI: http://dx.doi.org/10.1196/annals.1390.016.

74. Mura A, Feldon J. Spatial learning in rats is impaired after degeneration ofthe nigrostriatal dopaminergic system. Move Disord. 2003;18:860–71. DOI: http://dx.doi.org/10.1002/mds.10472.

75. Tamaru F. Disturbances in higher function in Parkinson's disease. J Eur Neurol. 1997;38(2):33–6.

76. DOI: http://dx.doi.org/10.1159/000113474.

77. Ridley RM, Cummings RM, Leow-Dyke A, Baker HF. Neglect of memory after dopaminergic lesions in monkeys. J Behav Brain Res. 2006;166:253–62. DOI: http://dx.doi.org/10. 1016/j.bbr.2005.08.007.

78. Giacino JT, Zacler ND. Outcome following severe brain injury: the comatose, vegetative and minimally responsive patient. J Head Traum Rehabil. 1995;10(1):40–56. DOI: http://dx.doi.org/10.1097/00001199-199502000-00006.