Zusammenfassung
Seit fast 20 Jahren wird eine mögliche Bedeutung des Kleinhirns für nichtmotorische Funktionen diskutiert. Aus den Befunden einer stetig zunehmenden Zahl von Läsions- und funktionellen Bildgebungsstudien wird eine Rolle des Kleinhirns für Sprache, visuell-räumliche Leistungen, Exekutivfunktionen einschließlich des Arbeitsgedächtnisses und für Aufmerksamkeit sowie Affekt und Verhalten abgeleitet. Für eine Reihe psychiatrischer Erkrankungen, z. B. für Autismus und Schizophrenie, wird ein Zusammenhang zwischen strukturellen Anomalien des Kleinhirns und Krankheitssymptomen angenommen. Inwieweit das Kleinhirn für kognitive Prozesse eine Rolle spielt und ob sich daraus eine klinische Relevanz ergibt, ist nach wie vor umstritten. Eine Reihe häufig zitierter Befunde, z. B. von bestimmten Aufmerksamkeits- und Sprachaufgaben, ließen sich in gut kontrollierten Studien nicht replizieren oder durch motorische Anteile der jeweiligen Aufgabe erklären. Neben dem Einfluss motorischer Defizite ist nicht abschließend geklärt, inwieweit unspezifische Ursachen, z. B. Hydrozephalus, Depression, aber auch globale Effekte auf den Hirnstoffwechsel neuropsychologische Testergebnisse, insbesondere bei fokalen Kleinhirnläsionen, erklären. Begleitende extrazerebelläre Läsionen sind nicht immer sicher auszuschließen. Auf der anderen Seite ist es durchaus möglich, dass das Kleinhirn spezifische Funktionen bei einem Teil kognitiver Aufgaben übernimmt. Ein gut untersuchtes Beispiel ist die Bedeutung des Kleinhirns für temporäre Aspekte bei der Sprachperzeption und -produktion einschließlich des inneren Sprechens. Ob die Beteiligung des Kleinhirns am inneren Sprechen und damit möglicherweise an allen Arbeitsgedächtnisaufgaben zu klinisch relevanten kognitiven Defiziten führt, ist nicht geklärt. Unabhängig von der Frage, ob nachweisbare Defizite primär auf die Schädigung des Kleinhirns zurückzuführen sind, ist es sinnvoll, bei Patienten mit Kleinhirnerkrankungen auf mögliche begleitende neuropsychologische Auffälligkeiten zu achten.
Abstract
Cerebellar involvement in a wide range of cognitive tasks, including language, visuo-spatial functions, attention, executive operations as well as affect and behaviour has been proposed almost 20 years ago. An increasing number of human lesion and functional brain imaging studies appear to support the hypothesis that the cerebellum contributes to non-motor functions. Likewise cognitive and behavioural changes in psychiatric disorders, such as autism and schizophrenia, have been linked to structural cerebellar abnormalities. The „cerebellum and cognition” hypothesis, however, is still a matter of ongoing controversial discussion. Frequently cited early findings, for example examining specific attention and language tasks, have not been replicated in later studies or have been explained by motor components of the tasks. In addition to impaired motor function, it is unclear to what extent deficits in neuropsychological tests are caused by unspecific effects, such as hydrocephalus, depression or global effects on brain metabolism, in particular following focal cerebellar lesions. Effects of extracerebellar lesions have to be considered, too. On the other hand, the cerebellum may be involved in specific operations in certain cognitive tasks. One example, which has been studied in detail, is a likely role of the cerebellum in the computation of temporal aspects of verbal utterances in the domains of both speech production, including inner speech, and speech perception. Whether disorders of inner speech are related to significant clinical signs of cognitive dysfunction remains to be determined. Regardless of the question whether possible cognitive deficits are caused primarily by cerebellar dysfunction, it appears useful to carefully assess neuropsychological functions in patients with cerebellar disorders.
Literatur
-
1
Leiner H C, Leiner A L, Dow R S.
Does the cerebellum contribute to mental skills?.
Behav Neurosci.
1986;
100
443-454
-
2
Leiner H C, Leiner A L, Dow R S.
Cognitive and language functions of the human cerebellum.
Trends Neurosci.
1993;
16
444-447
-
3
Schmahmann J D.
Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome.
J Neuropsychiatry Clin Neurosci.
2004;
16
367-378
-
4
Thach W T.
What is the role of the cerebellum in motor learning and cognition?.
Trends in Cognitive Sciences.
1998;
2
331-337
-
5
Schmahmann J D.
An emerging concept. The cerebellar contribution to higher function.
Arch Neurol.
1991;
48
1178-1187
-
6
Andreasen N C, O'Leary D S, Cizadlo T. et al .
Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry.
Proc Natl Acad Sci USA.
1996;
93
9985-9990
-
7
Schmahmann J D, Sherman J C.
The cerebellar cognitive affective syndrome.
Brain.
1998;
121
561-579
-
8
Riva D, Giorgi C.
The cerebellum contributes to higher functions during development: evidence from a series of children surgically treated for posterior fossa tumours.
Brain.
2000;
123
1051-1061
-
9
Scott R B, Stoodley C J, Anslow P. et al .
Lateralized cognitive deficits in children following cerebellar lesions.
Dev Med Child Neurol.
2001;
43
685-691
-
10
Middleton F A, Strick P L.
Cerebellar output channels.
Int Rev Neurobiol.
1997;
41
61-82
-
11
Cabeza R, Nyberg L.
Imaging cognition II: An empirical review of 275 PET and fMRI studies.
J Cogn Neurosci.
2000;
12
1-47
-
12
Allen G, Buxton R B, Wong E C. et al .
Attention activation of the cerebellum independent of motor involvement.
Science.
1997;
275
1940-1943
-
13
Petersen S E, Fox P T, Posner M I. et al .
Positron emission tomographic studies of the processing of single words.
J Cognit Neurosci.
1989;
1
153-170
-
14
Chen S H, Desmond J E.
Cerebrocerebellar networks during articulatory rehearsal and verbal working memory tasks.
Neuroimage.
2005;
24
332-338
-
15
Kirschen M P, Chen S H, Schraedley-Desmond P. et al .
Load- and practice-dependent increases in cerebro-cerebellar activation in verbal working memory: an fMRI study.
Neuroimage.
2005;
24
462-472
-
16
Kim S G, Ugurbil K, Strick P L.
Activation of a cerebellar output nucleus during cognitive processing.
Science.
1994;
265
949-951
-
17
Schall U, Johnston P, Lagopoulos J. et al .
Functional brain maps of Tower of London performance: a positron emission tomography and functional magnetic resonance imaging study.
Neuroimage.
2003;
20
1154-1161
-
18
Fink G R, Marshall J C, Shah N J. et al .
Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI.
Neurology.
2000;
54
1324-1331
-
19
Ho B C, Mola C, Andreasen N C.
Cerebellar dysfunction in neuroleptic naive schizophrenia patients: clinical, cognitive, and neuroanatomic correlates of cerebellar neurologic signs.
Biol Psychiatry.
2004;
55
1146-1153
-
20
Konarski J Z, McIntyre R S, Grupp L A. et al .
Is the cerebellum relevant in the circuitry of neuropsychiatric disorders?.
J Psychiatry Neurosci.
2005;
30
178-186
-
21
Courchesne E.
Brainstem, cerebellar and limbic neuroanatomical abnormalities in autism.
Curr Opin Neurobiol.
1997;
7
269-278
-
22
Nicolson R I, Fawcett A J, Dean P.
Developmental dyslexia: the cerebellar deficit hypothesis.
Trends Neurosci.
2001;
24
508-511
-
23
Roth R M, Saykin A J.
Executive dysfunction in attention-deficit/hyperactivity disorder: cognitive and neuroimaging findings.
Psychiatr Clin North Am.
2004;
27
83-96
-
24
Archibald C J, Wei X, Scott J N. et al .
Posterior fossa lesion volume and slowed information processing in multiple sclerosis.
Brain.
2004;
127
1526-1534
-
25
Allin M, Matsumoto H, Santhouse A M. et al .
Cognitive and motor function and the size of the cerebellum in adolescents born very pre-term.
Brain.
2001;
124
60-66
-
26
Dennis M, Edelstein K, Hetherington R. et al .
Neurobiology of perceptual and motor timing in children with spina bifida in relation to cerebellar volume.
Brain.
2004;
127
1292-1301
-
27
Lombardi W J, Woolston D J, Roberts J W. et al .
Cognitive deficits in patients with essential tremor.
Neurology.
2001;
57
785-790
-
28
Ackermann H, Mathiak K, Ivry R B.
Temporal organization of „internal speech” as a basis for cerebellar modulation of cognitive functions.
Behav Cogn Neurosci Rev.
2004;
3
14-22
-
29
Ivry R B, Spencer R M.
The neural representation of time.
Curr Opin Neurobiol.
2004;
14
225-232
-
30
Ito M.
Bases and implications of learning in the cerebellum - adaptive control and internal model mechanism.
Prog Brain Res.
2005;
148
95-109
-
31
Bower J M, Parsons L M.
Rethinking the „lesser brain”.
Sci Am.
2003;
289
50-57
-
32
Glickstein M.
Motor skills but not cognitive tasks.
Trends Neurosci.
1993;
16
450-451, Diskussion 453 - 454
-
33
Daum I, Ackermann H.
Neuropsychological abnormalities in cerebellar syndromes - fact or fiction?.
Int Rev Neurobiol.
1997;
41
455-471
-
34
Gibson K R.
Evolution of human intelligence: the roles of brain size and mental construction.
Brain Behav Evol.
2002;
59
10-20
-
35
Ungerleider L G, Haxby J V.
„What” and „where” in the human brain.
Curr Opin Neurobiol.
1994;
4
157-165
-
36
Gerwig M, Dimitrova A, Kolb F P. et al .
Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions.
Brain.
2003;
126
71-94
-
37
Hülsmann E, Erb M, Grodd W.
From will to action: sequential cerebellar contributions to voluntary movement.
Neuroimage.
2003;
20
1485-1492
-
38
Doyon J, Benali H.
Reorganization and plasticity in the adult brain during learning of motor skills.
Curr Opin Neurobiol.
2005;
15
161-167
-
39
Bloedel J R, Bracha V.
Duality of cerebellar motor and cognitive functions.
Int Rev Neurobiol.
1997;
41
613-634
-
40
Diamond A.
Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex.
Child Dev.
2000;
71
44-56
-
41
Corbetta M.
Frontoparietal cortical networks for directing attention and the eye to visual locations: identical, independent, or overlapping neural systems?.
Proc Natl Acad Sci USA.
1998;
95
831-838
-
42
Levisohn L, Cronin-Golomb A, Schmahmann J D.
Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population.
Brain.
2000;
123
1041-1050
-
43
Steinlin M, Imfeld S, Zulauf P. et al .
Neuropsychological long-term sequelae after posterior fossa tumour resection during childhood.
Brain.
2003;
126
1998-2008
-
44
Gottwald B, Wilde B, Mihajlovic Z. et al .
Evidence for distinct cognitive deficits after focal cerebellar lesions.
J Neurol Neurosurg Psychiatry.
2004;
75
1524-1531
-
45
Anderson S W, Damasio H, Tranel D.
Neuropsychological impairments associated with lesions caused by tumor or stroke.
Arch Neurol.
1990;
47
397-405
-
46
Konczak J, Schoch B, Dimitrova A, Timmann D.
Functional recovery of children and adolescents after cerebellar tumour resection.
Brain.
2005;
128
1428-1441
-
47
Malm J, Kristensen B, Karlsson T. et al .
Cognitive impairment in young adults with infratentorial infarcts.
Neurology.
1998;
51
433-440
-
48
Neau J P, Arroyo-Anllo E, Bonnaud V. et al .
Neuropsychological disturbances in cerebellar infarcts.
Acta Neurol Scand.
2000;
102
363-370
-
49
Exner C, Weniger G, Irle E.
Cerebellar lesions in the PICA but not SCA territory impair cognition.
Neurology.
2004;
63
2132-2135
-
50
Hoffmann M, Schmitt F.
Cognitive impairment in isolated subtentorial stroke.
Acta Neurol Scand.
2004;
109
14-24
-
51
Gomez Beldarrain M, Garcia-Monco J C, Quintana J M. et al .
Diaschisis and neuropsychological performance after cerebellar stroke.
Eur Neurol.
1997;
37
82-89
-
52
Dimitrov M, Grafman J, Kosseff P. et al .
Preserved cognitive processes in cerebellar degeneration.
Behav Brain Res.
1996;
79
131-135
-
53
Drepper J, Timmann D, Kolb F P. et al .
Non-motor associative learning in patients with isolated degenerative cerebellar disease.
Brain.
1999;
122
87-97
-
54
Arai M, Tanaka H, Pascual-Marqui R D. et al .
Reduced brain electric activities of frontal lobe in cortical cerebellar atrophy.
Clin Neurophysiol.
2003;
114
740-747
-
55
Globas C, Bosch S, Zühlke C. et al .
The cerebellum and cognition. Intellectual function in spinocerebellar ataxia type 6 (SCA6).
J Neurol.
2003;
250
1482-1487
-
56
Bürk K, Globas C, Bosch S. et al .
Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3.
J Neurol.
2003;
250
207-211
-
57
Bracke-Tolkmitt R, Linden A, Cananvan A GM. et al .
The cerebellum contributes to mental skills.
Behav Neurosci.
1989;
103
442-446
-
58
Molinari M, Petrosini L, Misciagna S. et al .
Visuospatial abilities in cerebellar disorders.
J Neurol Neurosurg Psychiatry.
2004;
75
235-240
-
59
Aarsen F K, Dongen H R Van, Paquier P F. et al .
Long-term sequelae in children after cerebellar astrocytoma surgery.
Neurology.
2004;
62
1311-1316
-
60
Ronning C, Sundet K, Due-Tonnessen B. et al .
Persistent cognitive dysfunction secondary to cerebellar injury in patients treated for posterior fossa tumors in childhood.
Pediatr Neurosurg.
2005;
41
15-21
-
61 Richter S, Schoch B, Kaiser O. et al .Children and adolescents with chronic cerebellar lesions show no clinical relevant signs of aphasia and neglect. J Neurophysiol 2005; Epub ahead of print
-
62
Karatekin C, Lazareff J A, Asarnow R F.
Relevance of the cerebellar hemispheres for executive functions.
Pediatr Neurol.
2000;
22
106-112
-
63
Pollack I F, Polinko P, Albright A L. et al .
Mutism and pseudobulbar symptoms after resection of posterior fossa tumors in children: incidence and pathophysiology.
Neurosurgery.
1995;
37
885-893
-
64
Ozimek A, Richter S, Hein-Kropp C. et al .
Cerebellar mutism - report of four cases.
J Neurol.
2004;
251
963-972
-
65
Catsman-Berrevoets C E, Dongen H R Van, Mulder P G. et al .
Tumour type and size are high risk factors for the syndrome of „cerebellar” mutism and subsequent dysarthria.
J Neurol Neurosurg Psychiatry.
1999;
67
755-757
-
66
Steinlin M, Styger M, Boltshauser E.
Cognitive impairments in patients with congenital nonprogressive cerebellar ataxia.
Neurology.
1999;
53
966-973
-
67
Guzzetta F, Mercuri E, Bonanno S. et al .
Autosomal recessive congenital cerebellar atrophy. A clinical and neuropsychological study.
Brain Dev.
1993;
15
439-445
-
68
Timmann D, Dimitrova A, Hein-Kropp C. et al .
Cerebellar agenesis: clinical, neuropsychological and MR findings.
Neurocase.
2003;
9
402-413
-
69
Richter S, Dimitrova A, Hein-Kropp C. et al .
Cerebellar agenesis II: motor and language functions.
Neurocase.
2005;
11
103-113
-
70
Eckert M A, Leonard C M, Wilke M. et al .
Anatomical signatures of dyslexia in children: unique information from manual and voxel based morphometry brain measures.
Cortex.
2005;
41
304-315
-
71
Ghaziuddin M, Butler E.
Clumsiness in autism and Asperger syndrome: a further report.
J Intellec Disabil Res.
1998;
42
43-48
-
72
Pitcher T M, Piek J P, Hay D A.
Fine and gross motor abilities in males with ADHD.
Dev Med Child Neurol.
2003;
45
525-535
-
73
Eliasson A-C, Rösblad B, Forssberg H.
Disturbances in programming goal-directed arm movements in children with ADHD.
Dev Med Child Neurol.
2004;
46
19-27
-
74
Takarae Y, Minshew N J, Luna B. et al .
Oculomotor abnormalities parallel cerebellar histopathology in autism.
J Neurol Neurosurg Psychiatry.
2004;
75
1359-1361
-
75
Fiez J A, Petersen S E, Cheney M K. et al .
Impaired non-motor learning and error detection associated with cerebellar damage. A single case study.
Brain.
1992;
115
155-178
-
76
Ackermann H, Wildgruber D, Daum I. et al .
Does the cerebellum contribute to cognitive aspects of speech production? A functional magnetic resonance imaging (fMRI) study in humans.
Neurosci Lett.
1998;
247
187-190
-
77
Helmuth L L, Ivry R B, Shimizu N.
Preserved performance by cerebellar patients on tests of word generation, discrimination learning, and attention.
Learn Mem.
1997;
3
456-474
-
78
Richter S, Kaiser O, Hein-Kropp C. et al .
Preserved verb generation in patients with cerebellar atrophy.
Neuropsychologia.
2004;
42
1235-1246
-
79
Silveri M C, Leggio M G, Molinari M.
The cerebellum contributes to linguistic production: a case of agrammatic speech following a right cerebellar lesion.
Neurology.
1994;
44
2047-2050
-
80
Marien P, Engelborghs S, Fabbro F. et al .
The lateralized linguistic cerebellum: a review and a new hypothesis.
Brain Lang.
2001;
79
580-600
-
81
Justus T.
The cerebellum and English grammatical morphology: evidence from production, comprehension, and grammaticality judgments.
J Cogn Neurosci.
2004;
16
1115-1130
-
82
Lalonde R, Strazielle C.
The effects of cerebellar damage on maze learning in animals.
Cerebellum.
2003;
2
300-309
-
83
Daum I, Ackermann H, Schugens M M. et al .
The cerebellum and cognitive functions in humans.
Behav Neurosci.
1993;
107
411-419
-
84
Appollonio I M, Grafman J, Schwartz V. et al .
Memory in patients with cerebellar degeneration.
Neurology.
1993;
43
1536-1544
-
85 Karnath H O. Neglect. In: Karnath HO, Thier P (Hrsg) Neuropsychologie. Heidelberg; Springer-Verlag 2003: 217-230
-
86
Silveri M C, Misciagna S, Terrezza G.
Right side neglect in right cerebellar lesion.
J Neurol Neurosurg Psychiatry.
2001;
71
114-117
-
87
Leggio M G, Silveri M C, Petrosini L. et al .
Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study.
J Neurol Neurosurg Psychiatry.
2000;
69
102-106
-
88
Witt K, Nuhsman A, Deuschl G.
Intact artificial grammar learning in patients with cerebellar degeneration and advanced Parkinson's disease.
Neuropsychologia.
2002;
40
1534-1540
-
89
Grafman J, Litvan I, Massaquoi S. et al .
Cognitive planning deficit in patients with cerebellar atrophy.
Neurology.
1992;
42
1493-1496
-
90
Heyder K, Suchan B, Daum I.
Cortico-subcortical contributions to executive control.
Acta Psychol (Amst).
2004;
115
271-289
-
91
Baddeley A.
Working memory: looking back and looking forward.
Nat Rev Neurosci.
2003;
4
829-839
-
92
Silveri M C, Betta A M Di, Filippini V. et al .
Verbal short-term store-rehearsal system and the cerebellum. Evidence from a patient with a right cerebellar lesion.
Brain.
1998;
121
2175-2187
-
93
Richter S, Matthies K, Ohde T. et al .
Stimulus-response versus stimulus-stimulus-response learning in cerebellar patients.
Exp Brain Res.
2004;
158
438-449
-
94
Gerwig M, Hajjar K, Dimitrova A. et al .
Timing of conditioned eyeblink responses is impaired in cerebellar patients.
J Neurosci.
2005;
25
3919-3931
-
95
Hetherington R, Dennis M, Spiegler B.
Perception and estimation of time in long-term survivors of childhood posterior fossa tumors.
J Int Neuropsychol Soc.
2000;
6
682-692
-
96
Harrington D L, Lee R R, Boyd L A. et al .
Does the representation of time depend on the cerebellum? Effect of cerebellar stroke.
Brain.
2004;
127
561-574
-
97
Akshoomoff N A, Courchesne E.
A new role for the cerebellum in cognitive operations.
Behav Neurosci.
1992;
106
731-738
-
98
Ravizza S M, Ivry R B.
Comparison of the basal ganglia and cerebellum in shifting attention.
J Cogn Neurosci.
2001;
13
285-297
-
99
Bischoff-Grethe A, Ivry R B, Grafton S T.
Cerebellar involvement in response reassignment rather than attention.
J Neurosci.
2002;
22
546-553
-
100
Schoch B, Gorissen B, Richter S. et al .
Do children with focal cerebellar lesions show deficits in shifting attention?.
J Neurophysiol.
2004;
92
1856-1866
-
101
Townsend J, Courchesne E, Covington J. et al .
Spatial attention deficits in patients with acquired or developmental cerebellar abnormality.
J Neurosci.
1999;
19
5632-5643
-
102
Golla H, Thier P, Haarmeier T.
Disturbed overt but normal covert shifts of attention in adult cerebellar patients.
Brain.
2005;
128
1525-1535
-
103
Gottwald B, Mihajlovic Z, Wilde B, Mehdorn H M.
Does the cerebellum contribute to specific aspects of attention?.
Neuropsychologia.
2003;
41
1452-1460
-
104
Canavan A G, Sprengelmeyer R, Diener H-C. et al .
Conditional associative learning is impaired in cerebellar disease in humans.
Behav Neurosci.
1994;
108
475-485
-
105
Tucker J, Harding A E, Jahanshahi M. et al .
Associative learning in patients with cerebellar ataxia.
Behav Neurosci.
1996;
110
1229-1234
-
106
Timmann D, Drepper J, Maschke M. et al .
Motor deficits cannot explain impaired cognitive associative learning in cerebellar patients.
Neuropsychologia.
2002;
40
788-800
-
107
Timmann D, Drepper J, Calabrese S. et al .
Use of sequence information in associative learning in control subjects and cerebellar patients.
Cerebellum.
2004;
3
75-82
-
108
Frings M, Boenisch R, Gerwig M. et al .
Learning of sensory sequences in cerebellar patients.
Learn Mem.
2004;
11
347-355
-
109
Nixon P D, Passingham R E.
The cerebellum and cognition: cerebellar lesions do not impair spatial working memory or visual associative learning in monkeys.
Eur J Neurosci.
1999;
11
4070-4080
-
110
Seidler R D, Purushotham A, Kim S G. et al .
Cerebellum activation associated with performance change but not motor learning.
Science.
2002;
296
2043-2046
-
111
Miall R C, Weir D J, Wolpert D M. et al .
Is the Cerebellum a Smith Predictor?.
J Mot Behav.
1993;
25
203-216
-
112
Courchesne E, Allen G.
Prediction and preparation, fundamental functions of the cerebellum.
Learn Mem.
1997;
4
1-35
-
113
Imamizu H, Kuroda T, Miyauchi S. et al .
Modular organization of internal models of tools in the human cerebellum.
Proc Natl Acad Sci USA.
2003;
100
5461-5466
-
114
Wolpert D M, Kawato M.
Multiple paired forward and inverse models for motor control.
Neural Netw.
1998;
11
1317-1329
-
115
Bloedel J R.
Task-dependent role of the cerebellum in motor learning.
Prog Brain Res.
2004;
143
319-329
-
116
Mathiak K, Hertrich I, Grodd W. et al .
Cerebellum and speech perception: a functional magnetic resonance study.
J Cogn Neurosci.
2002;
14
902-912
Prof. Dr. med. Dagmar Timmann
Neurologische Klinik · Universität Duisburg-Essen
Hufelandstraße 55
45138 Essen
eMail: Dagmar.Timmann@uni-essen.de
