Exekutive Kontrollfunktionen und Neuropsychiatrische Erkrankungen - Perspektiven für Forschung und Klinik

Zusammenfassung

Exekutive Kontrollfunktionen sind höhere kognitive Funktionen für komplexes zielgerichtetes Verhalten in Situationen, in denen Routinemechanismen nicht vorhanden oder nicht adäquat sind. Klinisch äußern sich exekutive Störungen außer in kognitiven Funktionen auch in Sozialverhalten und Antrieb. Exekutive Kontrollfunktionen basieren auf intakten Netzwerken zwischen präfrontalem Kortex und subkortikalen Strukturen, die in ihrer Funktion durch monoaminerge Neurotransmitter moduliert werden. Defizite exekutiver Kontrolle sind bei verschiedenen neuropsychiatrischen Erkrankungen beschrieben worden. Wir geben eine Übersicht über die Befunde mit einem Fokus auf extrapyramidale Bewegungsstörungen, Schizophrenie und affektive Störungen. Ein Schwerpunkt liegt dabei auf Gemeinsamkeiten zwischen diesen Erkrankungen hinsichtlich der Pathophysiologie fronto-subkortikaler Netzwerke. Aufgrund dieser Gemeinsamkeiten können Grundlinien pharmakologischer und rehabilitativer Strategien nosologieübergreifend auf die Behandlung exekutiver Defizite bei verschiedenen neuropsychiatrischen Krankheitsbildern angewendet werden. Wegen der hohen prognostischen Relevanz exekutiver Defizite sind kontrollierte Studien dieser Therapieverfahren dringend erforderlich.

Abstract

Executive control functions are higher cognitive functions for complex goal-oriented behavior in situations where routine mechanisms are not available or inappropriate. In clinical practice executive dysfunction presents with deficits in cognitive function as well as social behavior and drive. Executive control functions rely on intact networks involving prefrontal cortex and subcortical structures, which can be modulated by monoaminergic neurotransmitters. Deficits of executive control have been described in a variety of neuropsychiatric disorders. We present a review of the findings with a focus on movement disorders, schizophrenia and affective disorders. We emphasize similarities between these disorders regarding the pathophysiology of fronto-subcortical networks. Based on these similarities, principles of pharmacological and rehabilitative strategies can be applied to the treatment of executive deficits in a variety of neuropsychiatric disorders without being specific for one disease. Since executive dysfunction is highly relevant to prognosis, controlled trials of these treatments are urgently needed.

Literatur

• 1 Schneider W, Shiffrin R M. Controlled and automatic human information processing I: Detection, search and attention.  Psychol Rev. 1977;  84 1-66
• 2 Shiffrin R M, Schneider W. Controlled and automatic human information processing: II. Perceptual learning, automatic attending and a general theory.  Psychol Rev. 1977;  84 127-190
• 3 Hasher L, Zacks R T. Automatic and effortful processes in memory.  J Exp Psychol Gen. 1979;  108 356-389
• 4 Norman D A, Shallice T. Attention to action: Willed and automatic control of behavior. In: Davidson R, Schwartz G, Shapiro D (Hrsg). Consciousness and self-regulation. New York: Plenum Press 1986: 1-18
• 5 Stuss D T, Benson D F. The Frontal Lobes. New York: Raven 1986
• 6 Robbins T W. Dissociating executive functions of the prefrontal cortex.  Philos Trans R Soc Lond B Biol Sci. 1996;  351 (1346) 1463-1470
• 7 Stuss D T, Shallice T, Alexander M P, Picton T W. A multidisciplinary approach to anterior attentional functions.  Ann N Y Acad Sci. 1995;  769 191-211
• 8 Shallice T, Burgess P. The domain of supervisory processes and temporal organization of behaviour.  Philos Trans R Soc Lond B Biol Sci. 1996;  351 (1346) 1405-1411; discussion 1411 - 1412
• 9 Royall D R, Lauterbach E C, Cummings J L, Reeve A, Rummans T A, Kaufer D I, LaFrance Jr W C, Coffey C E. Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association.  J Neuropsychiatry Clin Neurosci. 2002;  14 (4) 377-405
• 10 Alexander G E, DeLong M R, Strick P L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex.  Annu Rev Neurosci. 1986;  9 357-381
• 11 Goldman-Rakic P S. Circuitry of primate prefrontal cortex and regulation of behavior by representational knowledge. In: Plum F, Mountcastle V (Hrsg). Handbook of Physiology. Bethesda: American Physiological Society 1987: 373-417
• 12 Mega M S, Cummings J L. Frontal-subcortical circuits and neuropsychiatric disorders.  J Neuropsychiatry Clin Neurosci. 1994;  6 (4) 358-370
• 13 Alexander G E, Crutcher M D. Functional architecture of basal ganglia circuits: neural substrates of parallel processing.  Trends Neurosci. 1990;  13 (7) 266-271
• 14 Graybiel A M. The basal ganglia.  Curr Biol. 2000;  10 (14) R509-511
• 15 Arnsten A F. Catecholamine regulation of the prefrontal cortex.  J Psychopharmacol. 1997;  11 (2) 151-162
• 16 Tekin S, Cummings J L. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update.  J Psychosom Res. 2002;  53 (2) 647-654
• 17 Berman K F, Ostrem J L, Randolph C, Gold J, Goldberg T E, Coppola R, Carson R E, Herscovitch P, Weinberger D R. Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study.  Neuropsychologia. 1995;  33 (8) 1027-1046
• 18 D'Esposito M, Detre J A, Alsop D C, Shin R K, Atlas S, Grossman M. The neural basis of the central executive system of working memory.  Nature. 1995;  378 (6554) 279-281
• 19 Bechara A, Damasio H, Damasio A R. Emotion, decision making and the orbitofrontal cortex.  Cereb Cortex. 2000;  10 (3) 295-307
• 20 Drewe E A. Go-Nogo learning after frontal lobe lesions in humans.  Cortex. 1975;  11 8-16
• 21 Starkstein S E, Robinson R G. Mechanism of disinhibition after brain lesions.  J Nerv Ment Dis. 1997;  185 (2) 108-114
• 22 Posner M I, DiGirolamo G. Executive attention: Conflict, target detection and cognitive control. In: Parasuraman R (Hrsg). The attentive brain. Cambridge: MIT Press 1998: 401-423
• 23 Cohen R A, Kaplan R F, Moser D J, Jenkins M A, Wilkinson H. Impairments of attention after cingulotomy.  Neurology. 1999;  53 (4) 819-824
• 24 Barch D M, Carter C S, Hachten P C, Usher M, Cohen J D. The „benefits” of distractibility: mechanisms underlying increased Stroop effects in schizophrenia.  Schizophr Bull. 1999;  25 (4) 749-762
• 25 Swerdlow N R, Koob G F. Dopamine, schizophrenia, mania and depression: Toward a unified hypothesis of cortico-striato-pallido-thalamic function.  Behav Brain Sci. 1987;  10 197-245
• 26 Heimer L. A new anatomical framework for neuropsychiatric disorders and drug abuse.  Am J Psychiatry. 2003;  160 (10) 1726-1739
• 27 Ovsiew F, Bylsma F W. The three cognitive examinations.  Semin Clin Neuropsychiatry. 2002;  7 (1) 54-64
• 28 Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a Frontal Assessment Battery at bedside.  Neurology. 2000;  55 (11) 1621-1626
• 29 Ring H A, Serra-Mestres J. Neuropsychiatry of the basal ganglia.  J Neurol Neurosurg Psychiatry. 2002;  72 (1) 12-21
• 30 Pirozzolo F J, Hansch E C, Mortimer J A, Webster D D, Kuskowski M A. Dementia in Parkinson disease: a neuropsychological analysis.  Brain Cogn. 1982;  1 (1) 71-83
• 31 Hietanen M, Teravainen H. Cognitive performance in early Parkinson's disease.  Acta Neurol Scand. 1986;  73 (2) 151-159
• 32 Lees A J, Smith E. Cognitive deficits in the early stages of Parkinson's disease.  Brain. 1983;  106 (Pt 2) 257-270
• 33 Kaasinen V, Rinne J O. Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease.  Neurosci Biobehav Rev. 2002;  26 (7) 785-793
• 34 Brown R G, Marsden C D. How common is dementia in Parkinson's disease?.  Lancet. 1984;  2 (8414) 1262-1265
• 35 Mortimer J A, Pirozzolo F J, Hansch E C, Webster D D. Relationship of motor symptoms to intellectual deficits in Parkinson disease.  Neurology. 1982;  32 (2) 133-137
• 36 Cooper J A, Sagar H J, Jordan N, Harvey N S, Sullivan E V. Cognitive impairment in early, untreated Parkinson's disease and its relationship to motor disability.  Brain. 1991;  114 ( Pt 5) 2095-2122
• 37 Dubois B, Pillon B. Cognitive deficits in Parkinson's disease.  J Neurol. 1997;  244 (1) 2-8
• 38 Muller U, Wachter T, Barthel H, Reuter M, Cramon D Y von. Striatal [123I]beta-CIT SPECT and prefrontal cognitive functions in Parkinson's disease.  J Neural Transm. 2000;  107 (3) 303-319
• 39 Cooper J A, Sagar H J, Doherty S M, Jordan N, Tidswell P, Sullivan E V. Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. A follow-up study of untreated patients.  Brain. 1992;  115 ( Pt 6) 1701-1725
• 40 Lange K W, Robbins T W, Marsden C D, James M, Owen A M, Paul G M. L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction.  Psychopharmacology (Berl). 1992;  107 (2 - 3) 394-404
• 41 Hietanen M, Teravainen H. Dementia and treatment with L-dopa in Parkinson's disease.  Mov Disord. 1988;  3 (3) 263-270
• 42 Robbins T W, James M, Owen A M, Lange K W, Lees A J, Leigh P N, Marsden C D, Quinn N P, Summers B A. Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.  J Neurol Neurosurg Psychiatry. 1994;  57 (1) 79-88
• 43 Blin J, Baron J C, Dubois B, Pillon B, Cambon H, Cambier J, Agid Y. Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations.  Arch Neurol. 1990;  47 (7) 747-752
• 44 Lange K W, Sahakian B J, Quinn N P, Marsden C D, Robbins T W. Comparison of executive and visuospatial memory function in Huntington's disease and dementia of Alzheimer type matched for degree of dementia.  J Neurol Neurosurg Psychiatry. 1995;  58 (5) 598-606
• 45 Lawrence A D, Sahakian B J, Hodges J R, Rosser A E, Lange K W, Robbins T W. Executive and mnemonic functions in early Huntington's disease.  Brain. 1996;  119 (Pt 5) 1633-1645
• 46 Backman L, Robins-Wahlin T B, Lundin A, Ginovart N, Farde L. Cognitive deficits in Huntington's disease are predicted by dopaminergic PET markers and brain volumes.  Brain. 1997;  120 (Pt 12) 2207-2217
• 47 Morice R, Delahunty A. Frontal/executive impairments in schizophrenia.  Schizophr Bull. 1996;  22 (1) 125-137
• 48 Heinrichs R W, Awad A G. Neurocognitive subtypes of chronic schizophrenia.  Schizophr Res. 1993;  9 (1) 49-58
• 49 Velligan D I, Bow-Thomas C C. Executive function in schizophrenia.  Semin Clin Neuropsychiatry. 1999;  4 (1) 24-33
• 50 Evans J J, Chua S E, McKenna P J, Wilson B A. Assessment of the dysexecutive syndrome in schizophrenia.  Psychol Med. 1997;  27 (3) 635-646
• 51 Franke P, Maier W, Hain C, Klingler T. Wisconsin Card Sorting Test: an indicator of vulnerability to schizophrenia?.  Schizophr Res. 1992;  6 (3) 243-249
• 52 Cannon T D, Huttunen M O, Lonnqvist J, Tuulio-Henriksson A, Pirkola T, Glahn D, Finkelstein J, Hietanen M, Kaprio J, Koskenvuo M. The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia.  Am J Hum Genet. 2000;  67 (2) 369-382
• 53 Weinberger D R, Egan M F, Bertolino A, Callicott J H, Mattay V S, Lipska B K, Berman K F, Goldberg T E. Prefrontal neurons and the genetics of schizophrenia.  Biol Psychiatry. 2001;  50 (11) 825-844
• 54 Pantelis C, Maruff P. The cognitive neuropsychiatric approach to investigating the neurobiology of schizophrenia and other disorders.  J Psychosom Res. 2002;  53 (2) 655-664
• 55 Kolb B, Whishaw I Q. Performance of schizophrenic patients on tests sensitive to left or right frontal, temporal, or parietal function in neurological patients.  J Nerv Ment Dis. 1983;  171 (7) 435-443
• 56 Morrison-Stewart S L, Williamson P C, Corning W C, Kutcher S P, Snow W G, Merskey H. Frontal and non-frontal lobe neuropsychological test performance and clinical symptomatology in schizophrenia.  Psychol Med. 1992;  22 (2) 353-359
• 57 Morris R G, Rushe T, Woodruffe P W, Murray R M. Problem solving in schizophrenia: a specific deficit in planning ability.  Schizophr Res. 1995;  14 (3) 235-246
• 58 Park S, Holzman P S. Schizophrenics show spatial working memory deficits.  Arch Gen Psychiatry. 1992;  49 (12) 975-982
• 59 Wexler B E, Stevens A A, Bowers A A, Sernyak M J, Goldman-Rakic P S. Word and tone working memory deficits in schizophrenia.  Arch Gen Psychiatry. 1998;  55 (12) 1093-1096
• 60 Pearlson G D, Marsh L. Structural brain imaging in schizophrenia: a selective review.  Biol Psychiatry. 1999;  46 (5) 627-649
• 61 Falkai P, Vogeley K, Maier W. Hirnstrukturelle Veränderungen bei Patienten mit schizophrenen Psychosen - Von der fokalen Pathologie zur Netzwerkstörung.  Nervenarzt. 2001;  72 (5) 331-341
• 62 Weinberger D R, Berman K F, Zec R F. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence.  Arch Gen Psychiatry. 1986;  43 (2) 114-124
• 63 Carter C S, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen J D. Functional hypofrontality and working memory dysfunction in schizophrenia.  Am J Psychiatry. 1998;  155 (9) 1285-1287
• 64 Curtis V A, Bullmore E T, Brammer M J, Wright I C, Williams S C, Morris R G, Sharma T S, Murray R M, McGuire P K. Attenuated frontal activation during a verbal fluency task in patients with schizophrenia.  Am J Psychiatry. 1998;  155 (8) 1056-1063
• 65 Orzack M H, Kornetsky C. Attention dysfunction in chronic schizophrenia.  Arch Gen Psychiatry. 1966;  14 323-326
• 66 Hepp H H, Maier S, Hermle L, Spitzer M. The Stroop effect in schizophrenic patients.  Schizophr Res. 1996;  22 (3) 187-195
• 67 Wykes T, Reeder C, Corner J. The prevalence and stability of an executive processing deficit, response inhibition, in people with chronic schizophrenia.  Schizophr Res. 2000;  46 (2 - 3) 241-253
• 68 Sanfilipo M, Lafargue T, Rusinek H, Arena L, Loneragan C, Lautin A, Feiner D, Rotrosen J, Wolkin A. Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms.  Arch Gen Psychiatry. 2000;  57 (5) 471-480
• 69 Wilder K E, Weinberger D R, Goldberg T E. Operant conditioning and the orbitofrontal cortex in schizophrenic patients: unexpected evidence for intact functioning.  Schizophr Res. 1998;  30 (2) 169-174
• 70 Hutton S B, Murphy F C, Joyce E M, Rogers R D, Cuthbert I, Barnes T R, McKenna P J, Sahakian B J, Robbins T W. Decision making deficits in patients with first-episode and chronic schizophrenia.  Schizophr Res. 2002;  55 (3) 249-257
• 71 Carter C S, Mintun M, Nichols T, Cohen J D. Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [15O]H₂O PET study during single-trial Stroop task performance.  Am J Psychiatry. 1997;  154 (12) 1670-1675
• 72 Rubia K, Russell T, Bullmore E T, Soni W, Brammer M J, Simmons A, Taylor E, Andrew C, Giampietro V, Sharma T. An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function.  Schizophr Res. 2001;  52 (1 - 2) 47-55
• 73 Fallgatter A J, Muller T J. Electrophysiological signs of reduced prefrontal response control in schizophrenic patients.  Psychiatry Res. 2001;  107 (1) 19-28
• 74 Weisbrod M, Kiefer M, Marzinzik F, Spitzer M. Executive control is disturbed in schizophrenia: evidence from event- related potentials in a Go/NoGo task.  Biol Psychiatry. 2000;  47 (1) 51-60
• 75 Hoff A L, Riordan H, O'Donnell D W, Morris L, DeLisi L E. Neuropsychological functioning of first-episode schizophreniform patients.  Am J Psychiatry. 1992;  149 (7) 898-903
• 76 Hutton S B, Puri B K, Duncan L J, Robbins T W, Barnes T R, Joyce E M. Executive function in first-episode schizophrenia.  Psychol Med. 1998;  28 (2) 463-473
• 77 Rund B R. A review of longitudinal studies of cognitive functions in schizophrenia patients.  Schizophr Bull. 1998;  24 (3) 425-435
• 78 Medalia A, Gold J M, Merriam A. The effects of neuroleptics on neuropsychological test results of schizophrenics.  Archives of Clinical Neuropsychology. 1988;  3 249-271
• 79 Verdoux H, Magnin E, Bourgeois M. Neuroleptic effects on neuropsychological test performance in schizophrenia.  Schizophr Res. 1995;  14 (2) 133-139
• 80 Keefe R S, Silva S G, Perkins D O, Lieberman J A. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis.  Schizophr Bull. 1999;  25 (2) 201-222
• 81 Nieuwenstein M R, Aleman A, de Haan E H. Relationship between symptom dimensions and neurocognitive functioning in schizophrenia: a meta-analysis of WCST and CPT studies. Wisconsin Card Sorting-Test. Continuous Performance-Test.  J Psychiatr Res. 2001;  35 (2) 119-125
• 82 Hughes C, Kumari V, Soni W, Das M, Binneman B, Drozd S, O'Neil S, Mathew V, Sharma T. Longitudinal study of symptoms and cognitive function in chronic schizophrenia.  Schizophr Res. 2002;  59 (2 - 3) 137-146
• 83 Robbins T W. The case of frontostriatal dysfunction in schizophrenia.  Schizophr Bull. 1990;  16 (3) 391-402
• 84 Buchanan R W, Strauss M E, Kirkpatrick B, Holstein C, Breier A, Carpenter Jr W T. Neuropsychological impairments in deficit vs nondeficit forms of schizophrenia.  Arch Gen Psychiatry. 1994;  51 (10) 804-811
• 85 Moore H, West A R, Grace A A. The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophrenia.  Biol Psychiatry. 1999;  46 (1) 40-55
• 86 Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y, Hwang D R, Keilp J, Kochan L, Heertum R van, Gorman J M, Laruelle M. Prefrontal dopamine D1-receptors and working memory in schizophrenia.  J Neurosci. 2002;  22 (9) 3708-3719
• 87 Friston K J. The disconnection hypothesis.  Schizophr Res. 1998;  30 (2) 115-125
• 88 Pantelis C, Barnes T R, Nelson H E, Tanner S, Weatherley L, Owen A M, Robbins T W. Frontal-striatal cognitive deficits in patients with chronic schizophrenia.  Brain. 1997;  120 ( Pt 10) 1823-1843
• 89 Jaeger J, Douglas E. Neuropsychiatric rehabilitation for persistent mental illness.  Psychiatr Q. 1992;  63 (1) 71-94
• 90 Green M F. What are the functional consequences of neurocognitive deficits in schizophrenia?.  Am J Psychiatry. 1996;  153 (3) 321-330
• 91 Velligan D I, Mahurin R K, Diamond P L, Hazleton B C, Eckert S L, Miller A L. The functional significance of symptomatology and cognitive function in schizophrenia.  Schizophr Res. 1997;  25 (1) 21-31
• 92 Breier A, Schreiber J L, Dyer J, Pickar D. National Institute of Mental Health longitudinal study of chronic schizophrenia. Prognosis and predictors of outcome.  Arch Gen Psychiatry. 1991;  48 (3) 239-246
• 93 Green M F, Nuechterlein K H. Should schizophrenia be treated as a neurocognitive disorder?.  Schizophr Bull. 1999;  25 (2) 309-319
• 94 Chowdhury R, Ferrier I N, Thompson J M. Cognitive dysfunction in bipolar disorder.  Curr Opin Psychiatry. 2003;  16 7-12
• 95 Austin M P, Mitchell P, Goodwin G M. Cognitive deficits in depression: possible implications for functional neuropathology.  Br J Psychiatry. 2001;  178 200-206
• 96 Bearden C E, Hoffman K M, Cannon T D. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review.  Bipolar Disord. 2001;  3 (3) 106-150; discussion 151 - 153
• 97 Purcell R, Maruff P, Kyrios M, Pantelis C. Neuropsychological function in young patients with unipolar major depression.  Psychol Med. 1997;  27 (6) 1277-1285
• 98 Merriam E P, Thase M E, Haas G L, Keshavan M S, Sweeney J A. Prefrontal cortical dysfunction in depression determined by Wisconsin Card Sorting-Test performance.  Am J Psychiatry. 1999;  156 (5) 780-782
• 99 Porter R J, Gallagher P, Thompson J M, Young A H. Neurocognitive impairment in drug-free patients with major depressive disorder.  Br J Psychiatry. 2003;  182 (3) 214-220
• 100 Landro N I, Stiles T C, Sletvold H. Neuropsychological function in nonpsychotic unipolar major depression.  Neuropsychiatry Neuropsychol Behav Neurol. 2001;  14 (4) 233-240
• 101 Videbech P. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review.  Acta Psychiatr Scand. 2000;  101 (1) 11-20
• 102 Trichard C, Martinot J L, Alagille M, Masure M C, Hardy P, Ginestet D, Feline A. Time course of prefrontal lobe dysfunction in severely depressed in patients: a longitudinal neuropsychological study.  Psychol Med. 1995;  25 (1) 79-85
• 103 Kaiser S, Unger J, Kiefer M, Markela J, Mundt C, Weisbrod M. Executive Control Deficit in Depression: Event-Related Potentials in a Go/Nogo Task.  Psychiatry Res Neuroimaging. 2003;  122 169-184
• 104 Degl'Innocenti A, Agren H, Backman L. Executive deficits in major depression.  Acta Psychiatr Scand. 1998;  97 (3) 182-188
• 105 Austin M P, Mitchell P, Wilhelm K, Parker G, Hickie I, Brodaty H, Chan J, Eyers K, Milic M, Hadzi-Pavlovic D. Cognitive function in depression: a distinct pattern of frontal impairment in melancholia?.  Psychol Med. 1999;  29 (1) 73-85
• 106 Dolan R J, Bench C J, Liddle P F, Friston K J, Frith C D, Grasby P M, Frackowiak R S. Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or disease specificity?.  J Neurol Neurosurg Psychiatry. 1993;  56 (12) 1290-1294
• 107 Dolan R J, Bench C J, Brown R G, Scott L C, Frackowiak R S. Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow.  Psychol Med. 1994;  24 (4) 849-857
• 108 Borkowska A, Rybakowski J K. Neuropsychological frontal lobe tests indicate that bipolar depressed patients are more impaired than unipolar.  Bipolar Disord. 2001;  3 (2) 88-94
• 109 Neu P, Kiesslinger U, Schlattmann P, Reischies F M. Time-related cognitive deficiency in four different types of depression.  Psychiatry Res. 2001;  103 (2 - 3) 237-247
• 110 Lockwood K A, Alexopoulos G S, Gorp W G van. Executive dysfunction in geriatric depression.  Am J Psychiatry. 2002;  159 (7) 1119-1126
• 111 Quraishi S, Frangou S. Neuropsychology of bipolar disorder: a review.  J Affect Disord. 2002;  72 (3) 209-226
• 112 Morice R. Cognitive inflexibility and pre-frontal dysfunction in schizophrenia and mania.  Br J Psychiatry. 1990;  157 50-54
• 113 Clark L, Iversen S D, Goodwin G M. A neuropsychological investigation of prefrontal cortex involvement in acute mania.  Am J Psychiatry. 2001;  158 (10) 1605-1611
• 114 Rubinsztein J S, Fletcher P C, Rogers R D, Ho L W, Aigbirhio F I, Paykel E S, Robbins T W, Sahakian B J. Decision-making in mania: a PET study.  Brain. 2001;  124 (Pt 12) 2550-2563
• 115 Paradiso S, Lamberty G J, Garvey M J, Robinson R G. Cognitive impairment in the euthymic phase of chronic unipolar depression.  J Nerv Ment Dis. 1997;  185 (12) 748-754
• 116 Clark L, Iversen S D, Goodwin G M. Sustained attention deficit in bipolar disorder.  Br J Psychiatry. 2002;  180 313-319
• 117 Zubieta J K, Huguelet P, O'Neil R L, Giordani B J. Cognitive function in euthymic bipolar I disorder.  Psychiatry Res. 2001;  102 (1) 9-20
• 118 Martinez-Aran A, Penades R, Vieta E, Colom F, Reinares M, Benabarre A, Salamero M, Gasto C. Executive function in patients with remitted bipolar disorder and schizophrenia and its relationship with functional outcome.  Psychother Psychosom. 2002;  71 (1) 39-46
• 119 Alexopoulos G S, Meyers B S, Young R C, Kalayam B, Kakuma T, Gabrielle M, Sirey J A, Hull J. Executive dysfunction and long-term outcomes of geriatric depression.  Arch Gen Psychiatry. 2000;  57 (3) 285-290
• 120 Dunkin J J, Leuchter A F, Cook I A, Kasl-Godley J E, Abrams M, Rosenberg-Thompson S. Executive dysfunction predicts nonresponse to fluoxetine in major depression.  J Affect Disord. 2000;  60 (1) 13-23
• 121 Kaiser S, Mundt C, Weisbrod M. Störung der exekutiven Kontrollfunktionen bei depressiven Patienten - Implikationen für die Psychotherapie. In: Schiepek G (Hrsg). Neurobiologie der Psychotherapie. Stuttgart: Schattauer 2003
• 122 Soares J C, Mann J J. The anatomy of mood disorders - review of structural neuroimaging studies.  Biol Psychiatry. 1997;  41 (1) 86-106
• 123 Ebert D, Lammers C-H. Das zentrale dopaminerge System und die Depression.  Nervenarzt. 1999;  68 545-555
• 124 Modell J G, Mountz J M, Curtis G C, Greden J F. Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder.  J Neuropsychiatry Clin Neurosci. 1989;  1 (1) 27-36
• 125 Saxena S, Brody A L, Schwartz J M, Baxter L R. Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder.  Br J Psychiatry Suppl. 1998;  (35) 26-37
• 126 Anderson K E, Savage C R. Cognitive and neurobiological findings in obsessive-compulsive disorder.  Psychiatr Clin North Am. 2004;  27 (1) 37-47, viii
• 127 Kuelz A K, Hohagen F, Voderholzer U. Neuropsychological performance in obsessive-compulsive disorder: a critical review.  Biol Psychol. 2004;  65 (3) 185-236
• 128 Evans D W, Lewis M D, Iobst E. The role of the orbitofrontal cortex in normally developing compulsive-like behaviors and obsessive-compulsive disorder.  Brain Cogn. 2004;  55 (1) 220-234
• 129 Basso M R, Bornstein R A, Carona F, Morton R. Depression accounts for executive function deficits in obsessive-compulsive disorder.  Neuropsychiatry Neuropsychol Behav Neurol. 2001;  14 (4) 241-245
• 130 Mataix-Cols D, Alonso P, Pifarre J, Menchon J M, Vallejo J. Neuropsychological performance in medicated vs. unmedicated patients with obsessive-compulsive disorder.  Psychiatry Res. 2002;  109 (3) 255-264
• 131 Nielen M M, Den Boer J A. Neuropsychological performance of OCD patients before and after treatment with fluoxetine: evidence for persistent cognitive deficits.  Psychol Med. 2003;  33 (5) 917-925
• 132 Kunert H J, Druecke H W, Sass H, Herpertz S C. Frontal lobe dysfunctions in borderline personality disorder? Neuropsychological findings.  J Personal Disord. 2003;  17 (6) 497-509
• 133 Monarch E S, Saykin A J, Flashman L A. Neuropsychological impairment in borderline personality disorder.  Psychiatr Clin North Am. 2004;  27 (1) 67-82, viii-ix
• 134 Bazanis E, Rogers R D, Dowson J H, Taylor P, Meux C, Staley C, Nevinson-Andrews D, Taylor C, Robbins T W, Sahakian B J. Neurocognitive deficits in decision-making and planning of patients with DSM-III-R borderline personality disorder.  Psychol Med. 2002;  32 (8) 1395-1405
• 135 Rentrop M, Unger J, Weisbrod M, Renneberg B. Response Inhibition in Borderline Personality Disorder: Performance in a Go/Nogo task. Eingereicht
• 136 Soloff P H, Meltzer C C, Becker C, Greer P J, Kelly T M, Constantine D. Impulsivity and prefrontal hypometabolism in borderline personality disorder.  Psychiatry Res. 2003;  123 (3) 153-163
• 137 Brower M C, Price B H. Neuropsychiatry of frontal lobe dysfunction in violent and criminal behaviour: a critical review.  J Neurol Neurosurg Psychiatry. 2001;  71 (6) 720-726
• 138 Dolan M, Park I. The neuropsychology of antisocial personality disorder.  Psychol Med. 2002;  32 (3) 417-427
• 139 Vollm B, Richardson P, Stirling J, Elliott R, Dolan M, Chaudhry I, Del Ben C, McKie S, Anderson I, Deakin B. Neurobiological substrates of antisocial and borderline personality disorder: preliminary results of a functional fMRI study.  Crim Behav Ment Health. 2004;  14 (1) 39-54
• 140 Coull J T. Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology.  Prog Neurobiol. 1998;  55 (4) 343-361
• 141 Robbins T W. Chemical neuromodulation of frontal-executive functions in humans and other animals.  Exp Brain Res. 2000;  133 (1) 130-138
• 142 Nieoullon A. Dopamine and the regulation of cognition and attention.  Prog Neurobiol. 2002;  67 (1) 53-83
• 143 Honey G D, Bullmore E T, Soni W, Varatheesan M, Williams S C, Sharma T. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia.  Proc Natl Acad Sci U S A. 1999;  96 (23) 13 432-13 437
• 144 Marin R S. Apathy: Concept, Syndrome, Neural Mechanisms, and Treatment.  Semin Clin Neuropsychiatry. 1996;  1 (4) 304-314
• 145 Meltzer H Y, Park S, Kessler R. Cognition, schizophrenia, and the atypical antipsychotic drugs.  Proc Natl Acad Sci U S A. 1999;  96 (24) 13 591-13 593
• 146 Friedman J I, Temporini H, Davis K L. Pharmacologic strategies for augmenting cognitive performance in schizophrenia.  Biol Psychiatry. 1999;  45 (1) 1-16
• 147 Lidow M S, Goldman-Rakic P S, Gallager D W, Rakic P. Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390.  Neuroscience. 1991;  40 (3) 657-671
• 148 Muller U, Cramon D Y von, Pollmann S. D1- versus D2-receptor modulation of visuospatial working memory in humans.  J Neurosci. 1998;  18 (7) 2720-2728
• 149 Roesch-Ely D, Scheffel H, Weiland S, Schwaninger M, Hundemer H P, Kolter T, Witte S, Weisbrod M. Dopaminergic Modulation of PFC functions in schizophrenic patients. Eingereicht
• 150 Kimberg D Y, D'Esposito M, Farah M J. Effects of bromocriptine on human subjects depend on working memory capacity.  Neuroreport. 1997;  8 (16) 3581-3585
• 151 Harvey P D, Keefe R S. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment.  Am J Psychiatry. 2001;  158 (2) 176-184
• 152 Richelson E. Pharmacology of antidepressants - characteristics of the ideal drug.  Mayo Clin Proc. 1994;  69 (11) 1069-1681
• 153 Arnsten A F, Steere J C, Hunt R D. The contribution of α₂-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder.  Arch Gen Psychiatry. 1996;  53 (5) 448-455
• 154 Moffoot A, O'Carroll R E, Murray C, Dougall N, Ebmeier K, Goodwin G M. Clonidine infusion increases uptake of 99mTc-Exametazime in anterior cingulate cortex in Korsakoff's psychosis.  Psychol Med. 1994;  24 (1) 53-61
• 155 Fields R B, Kammen D P van, Peters J L, Rosen J, Kammen W B van, Nugent A, Stipetic M, Linnoila M. Clonidine improves memory function in schizophrenia independently from change in psychosis. Preliminary findings.  Schizophr Res. 1988;  1 (6) 417-423
• 156 Ferguson J M, Wesnes K A, Schwartz G E. Reboxetine versus paroxetine versus placebo: effects on cognitive functioning in depressed patients.  Int Clin Psychopharmacol. 2003;  18 (1) 9-14
• 157 Meltzer H Y. The role of serotonin in antipsychotic drug action.  Neuropsychopharmacology. 1999;  21 (2 Suppl) 106S-115S
• 158 Rogers R D, Blackshaw A J, Middleton H C, Matthews K, Hawtin K, Crowley C, Hopwood A, Wallace C, Deakin J F, Sahakian B J, Robbins T W. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour.  Psychopharmacology (Berl). 1999;  146 (4) 482-491
• 159 Fava M. Psychopharmacologic treatment of pathologic aggression.  Psychiatr Clin North Am. 1997;  20 (2) 427-451
• 160 Hollander E, Rosen J. Impulsivity.  J Psychopharmacol. 2000;  14 (2 Suppl 1) S39-44
• 161 Kopelman M D. The cholinergic neurotransmitter system in human memory and dementia: a review.  Q J Exp Psychol A. 1986;  38 (4) 535-573
• 162 Everitt B, Robbins T W. Central cholinergic systems and cognition.  Annu Rev Psychol. 1996;  48 649-684
• 163 Cummings J L. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations.  Am J Geriatr Psychiatry. 2003;  11 (2) 131-145
• 164 Amenta F, Di Tullio M A, Tomassoni D. The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies.  Clin Exp Hypertens. 2002;  24 (7 - 8) 697-713
• 165 Griffin S L, Reekum R van, Masanic C. A review of cholinergic agents in the treatment of neurobehavioral deficits following traumatic brain injury.  J Neuropsychiatry Clin Neurosci. 2003;  15 (1) 17-26
• 166 Mateer C A. Executive function disorders: rehabilitation challenges and strategies.  Semin Clin Neuropsychiatry. 1999;  4 (1) 50-59
• 167 Gauggel S. Neuropsychologische Therapie der Frontalhirnstörung: Therapieprogramme. In: Foerstl H (Hrsg). Der Frontallappen. Funktionen und Erkrankungen. Berlin: Springer 2002
• 168 Backman L, Dixon R A. Psychological compensation: a theoretical framework.  Psychol Bull. 1992;  112 (2) 259-283
• 169 Campbell 3rd J J, Duffy J D, Salloway S P. Treatment strategies for patients with dysexecutive syndromes.  J Neuropsychiatry Clin Neurosci. 1994;  6 (4) 411-418
• 170 Sohlberg M M, Mateer C. Cognitive Rehabilitation - An Integrative Neuropsychological Approach. New York: Guilford Press 2001
• 171 Baddeley A D. Implicit memory and errorless learning: a link between cognitive theory and neuropsychological rehabilitation?. In: Squire LR, Buttes N (Hrsg). Neuropsychology of memory. 2. Aufl. New York: Guilford 1992: 309-314
• 172 Kern R S, Liberman R P, Kopelowicz A, Mintz J, Green M F. Applications of errorless learning for improving work performance in persons with schizophrenia.  Am J Psychiatry. 2002;  159 (11) 1921-1926
• 173 Meichenbaum D. The potential contributions of cognitive behavior modification to the rehabilitation of individuals with traumatic brain injury.  Semin Speech Lang. 1993;  14 (1) 18-31
• 174 Cicerone K D, Giacino J T. Remediation of executive function deficits.  Neurorehabilitation. 1992;  2 73-83
• 175 Cramon D Y von, Matthes-von Cramon G. Back to work with a chronic dysexecutive syndrome? A case report.  Neuropsychol Rehab. 1994;  4 399-417
• 176 Alderman N, Fry R K, Youngson H A. Improvement of self-monitoring skills, reduction of behavior disturbance and the dysexecutive syndrome: Comparison of response cost and a new programme of self-monitoring training.  Neuropsychol Rehab. 1995;  5 193-221
• 177 Robertson I H, Murre J M. Rehabilitation of brain damage: brain plasticity and principles of guided recovery.  Psychol Bull. 1999;  125 (5) 544-575
• 178 Cramon D Y von, Matthes-von Cramon G, Mai N. Problem-solving deficits in brain-injured patients: A therapeutic approach.  Neuropsychological Rehabilitation. 1991;  1 45-64
• 179 Sohlberg M M, Mateer C. Introduction to cognitive rehabilitation. New York: Guilford 1989
• 180 Vauth R, Dietl M, Stieglitz R D, Olbrich H M. Kognitive Remediation - Eine neue Chance in der Rehabilitation schizophrener Störungen?.  Nervenarzt. 2000;  71 (1) 19-29
• 181 Bellack A S, Gold J M, Buchanan R W. Cognitive rehabilitation for schizophrenia: problems, prospects, and strategies.  Schizophr Bull. 1999;  25 (2) 257-274
• 182 Delahunty A, Morice R. Rehabilitation of frontal/executive impairments in schizophrenia.  Aust N Z J Psychiatry. 1996;  30 (6) 760-767
• 183 Wykes T, Reeder C, Corner J, Williams C, Everitt B. The effects of neurocognitive remediation on executive processing in patients with schizophrenia.  Schizophr Bull. 1999;  25 (2) 291-307
• 184 Stablum F, Umilta C, Mogentale C, Carlan M, Guerrini C. Rehabilitation of executive deficits in closed head injury and anterior communicating artery aneurysm patients.  Psychological Research. 2000;  63 265-278
• 185 Sohlberg M M, Raskin S. Principles of generalization applied to attention and memory interventions.  Journal of Head Trauma Rehabilitation. 1996;  11 (2) 65-78
• 186 Grant D A, Berg E A. A behavioral analysis of the degree of reinforcement and ease of shifting to new responses in a Weigl-type card sorting problem.  J Exp Psychol. 1948;  38 404-411
• 187 Milner B. Effects of different brain lesions on card sorting.  Arch Neurol. 1963;  9 90-100
• 188 Jones-Gotman M, Milner B. Design fluency: the invention of nonsense drawings after focal cortical lesions.  Neuropsychologia. 1977;  15 633-674
• 189 Shallice T. Specific impairments of planning.  Philos Trans R Soc Lond B Biol Sci. 1982;  298 199-209
• 190 Porteus S D. Porteus Maze Test: Fifty Years' Application. Palo Alto: Pacific Books 1965
• 191 Oscar-Berman M, McNamara P, Freedman M. Delayed-response tasks: parallels between experimental ablation studies and findings in patients with frontal lesions. In: Benton A (Hrsg). Frontal Lobe Function and Dysfunction. New York: Oxford University Press 1991: 256-272
• 192 Nystrom L E, Braver T S, Sabb F W, Delgado M R, Noll D C, Cohen J D. Working memory for letters, shapes, and locations: fMRI evidence against stimulus-based regional organization in human prefrontal cortex.  Neuroimage. 2000;  11 (5 Pt 1) 424-446
• 193 Rosvold H E, Mirsky A, Sarason I, Bransome Jr E D, Beck L H. A continuous performance test of brain damage.  Journal of Consulting Psychology. 1956;  20 343-350
• 194 Stroop J. Studies of interference in serial verbal reactions.  J Exp Psychol. 1935;  18 643-662
• 195 Royall D R, Mahurin R K, Gray K F. Bedside assessment of executive cognitive impairment: the executive interview.  J Am Geriatr Soc. 1992;  40 (12) 1221-1226
• 196 Royall D R, Cordes J A, Polk M. CLOX: an executive clock drawing task.  J Neurol Neurosurg Psychiatry. 1998;  64 (5) 588-594
• 197 Grigsby J, Kaye K, Robbins L J. Reliabilities, norms and factor structure of the Behavioral Dyscontrol Scale.  Percept Mot Skills. 1992;  74 (3 Pt 1) 883-892
• 198 Grace J, Stout J C, Malloy P F. Frontal Systems Behavior Scale: Professional manual. Lutz, Florida: Psychological Assessment Resources 2001
• 199 Braswell D, Hartry A, Hoornbeek S, Johansen A, Johnson L, Schultz J, Sohlberg M M. Profile of the Executive Control System. Wake Forest: Lash & Associates 1993
• 200 Gauggel S, Deckersbach T, Rolko C. Entwicklung und erste Evaluation einer Skala zur Beurteilung von Handlungs-, Planungs- und Problemlösestörungen.  Z Neuropsychol. 1998;  11 (3) 159-171
• 201 Pechtold K, Jankowski P. Handeln lernen. München: Urban & Fischer 2000
• 202 Wilson B A, Aldermann N, Burgess P W. et al .The Behavioural Assessment of the Dysexecutive Syndrome. Flempton: Thames Valley Test Company 1996
• 203 Ettlin T M, Kischka U, Beckson M, Gaggiotti M, Rauchfleisch U, Benson D F. The Frontal Lobe Score: part I: construction of a mental status of frontal systems.  Clin Rehabil. 2000;  14 (3) 260-271