Skip to main content
Top
Published in: The Cerebellum 4/2008

01-12-2008

Lesion-Symptom Mapping of the Human Cerebellum

Authors: D. Timmann, B. Brandauer, J. Hermsdörfer, W. Ilg, J. Konczak, M. Gerwig, E. R. Gizewski, B. Schoch

Published in: The Cerebellum | Issue 4/2008

Login to get access

Abstract

High-resolution structural magnetic resonance imaging (MRI) has become a powerful tool in human cerebellar lesion studies. Structural MRI is helpful to analyse the localisation and extent of cerebellar lesions and to determine possible extracerebellar involvement. Functionally meaningful correlations between a cerebellar lesion site and behavioural data can be obtained both in subjects with degenerative as well as focal cerebellar disorders. In this review, examples are presented which demonstrate that MRI-based lesion-symptom mapping is helpful to study the function of cerebellar cortex and cerebellar nuclei. Behavioural measures were used which represent two main areas of cerebellar function, that is, motor coordination and motor learning. One example are correlations with clinical data which are in good accordance with the known functional compartmentalisation of the cerebellum in three sagittal zones: In patients with cerebellar cortical degeneration ataxia of stance and gait was correlated with atrophy of the medial (and intermediate) cerebellum, oculomotor disorders with the medial, dysarthria with the intermediate and limb ataxia with atrophy of the intermediate and lateral cerebellum. Similar findings were obtained in patients with focal lesions. In addition, in patients with acute focal lesions, a somatotopy in the superior cerebellar cortex was found which is in close relationship to animal data and functional MRI data in healthy control subjects. Finally, comparison of data in patients with acute and chronic focal lesions revealed that lesion site appears to be critical for motor recovery. Recovery after lesions to the nuclei of the cerebellum was less complete. Another example which extended knowledge about functional localisation within the cerebellum is classical conditioning of the eyeblink response, a simple form of motor learning. In healthy subjects, learning rate was related to the volume of the cortex of the posterior cerebellar lobe. In patients with focal cerebellar lesions, acquisition of eyeblink conditioning was significantly reduced in lesions including the cortex of the superior posterior lobe, but not the inferior posterior lobe. Disordered timing of conditioned eyeblink responses correlated with lesions of the anterior lobe. Findings are in good agreement with the animal literature. Different parts of the cerebellar cortex may be involved in acquisition and timing of conditioned eyeblink responses in humans. These examples demonstrate that MRI-based lesion-symptom mapping is helpful to study the contribution of functionally relevant cerebellar compartments in motor control and recovery in patients with cerebellar disease. In addition, information about the function of cerebellar cortex and nuclei can be gained.
Literature
1.
go back to reference Rorden C, Karnath HO (2004) Using human brain lesions to infer function: a relic from a past era in the fMRI age. Nat Rev Neurosci 5:813–819, ReviewPubMedCrossRef Rorden C, Karnath HO (2004) Using human brain lesions to infer function: a relic from a past era in the fMRI age. Nat Rev Neurosci 5:813–819, ReviewPubMedCrossRef
2.
go back to reference Makris N, Schlerf JE, Hodge SM, Haselgrove C, Albaugh MD, Seidman LJ, Rauch SL, Harris G, Biederman J, Caviness VS, Kennedy DN, Schmahmann JD (2005) MRI-based surface-assisted parcellation of human cerebellar cortex: an anatomically specified method with estimate of reliability. Neuroimage 25:1146–1160PubMedCrossRef Makris N, Schlerf JE, Hodge SM, Haselgrove C, Albaugh MD, Seidman LJ, Rauch SL, Harris G, Biederman J, Caviness VS, Kennedy DN, Schmahmann JD (2005) MRI-based surface-assisted parcellation of human cerebellar cortex: an anatomically specified method with estimate of reliability. Neuroimage 25:1146–1160PubMedCrossRef
3.
go back to reference Gerwig M, Dimitrova A, Kolb FP, Maschke M, Brol B, Kunnel A, Böring D, Thilmann AF, Forsting M, Diener HC, Timmann D (2003) Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions. Brain 126:71–94PubMedCrossRef Gerwig M, Dimitrova A, Kolb FP, Maschke M, Brol B, Kunnel A, Böring D, Thilmann AF, Forsting M, Diener HC, Timmann D (2003) Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions. Brain 126:71–94PubMedCrossRef
4.
go back to reference Dimitrova A, Weber J, Redies C, Kindsvater K, Maschke M, Kolb FP, Forsting M, Diener HC, Timmann D (2002) MRI atlas of the human cerebellar nuclei. Neuroimage 17:240–255PubMedCrossRef Dimitrova A, Weber J, Redies C, Kindsvater K, Maschke M, Kolb FP, Forsting M, Diener HC, Timmann D (2002) MRI atlas of the human cerebellar nuclei. Neuroimage 17:240–255PubMedCrossRef
5.
go back to reference Dimitrova A, Zeljko D, Schwarze F, Maschke M, Gerwig M, Frings M, Beck A, Aurich V, Forsting M, Timmann D (2006) Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei. Neuroimage 30:12–25PubMedCrossRef Dimitrova A, Zeljko D, Schwarze F, Maschke M, Gerwig M, Frings M, Beck A, Aurich V, Forsting M, Timmann D (2006) Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei. Neuroimage 30:12–25PubMedCrossRef
6.
go back to reference Diedrichsen J (2006) A spatially unbiased atlas template of the human cerebellum. Neuroimage 33:127–138PubMedCrossRef Diedrichsen J (2006) A spatially unbiased atlas template of the human cerebellum. Neuroimage 33:127–138PubMedCrossRef
7.
go back to reference Deoni SC, Catani M (2007) Visualization of the deep cerebellar nuclei using quantitative T1 and rho magnetic resonance imaging at 3 Tesla. Neuroimage 37:1260–1266PubMedCrossRef Deoni SC, Catani M (2007) Visualization of the deep cerebellar nuclei using quantitative T1 and rho magnetic resonance imaging at 3 Tesla. Neuroimage 37:1260–1266PubMedCrossRef
8.
go back to reference Rorden C, Karnath HO, Bonilha L (2007) Improving lesion-symptom mapping. J Cogn Neurosci 19:1081–1088PubMedCrossRef Rorden C, Karnath HO, Bonilha L (2007) Improving lesion-symptom mapping. J Cogn Neurosci 19:1081–1088PubMedCrossRef
9.
go back to reference Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, Dronkers NF (2003) Voxel-based lesion-symptom mapping. Nat Neurosci 6:448–450PubMed Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, Dronkers NF (2003) Voxel-based lesion-symptom mapping. Nat Neurosci 6:448–450PubMed
10.
go back to reference Lasek K, Lencer R, Gaser C, Hagenah J, Walter U, Wolters A, Kock N, Steinlechner S, Nagel M, Zühlke C, Nitschke MF, Brockmann K, Klein C, Rolfs A, Binkofski F (2006) Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17). Brain 129:2341–2345PubMedCrossRef Lasek K, Lencer R, Gaser C, Hagenah J, Walter U, Wolters A, Kock N, Steinlechner S, Nagel M, Zühlke C, Nitschke MF, Brockmann K, Klein C, Rolfs A, Binkofski F (2006) Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17). Brain 129:2341–2345PubMedCrossRef
11.
go back to reference Shallice T (1988) From neuropsychology to mental structure. Cambridge University Press, Cambridge Shallice T (1988) From neuropsychology to mental structure. Cambridge University Press, Cambridge
12.
go back to reference Richter S, Dimitrova A, Maschke M, Gizewski E, Beck A, Aurich V, Timmann D (2005) Degree of cerebellar ataxia correlates with three-dimensional MRI-based cerebellar volume in pure cerebellar degeneration. Eur Neurol 54:23–27PubMedCrossRef Richter S, Dimitrova A, Maschke M, Gizewski E, Beck A, Aurich V, Timmann D (2005) Degree of cerebellar ataxia correlates with three-dimensional MRI-based cerebellar volume in pure cerebellar degeneration. Eur Neurol 54:23–27PubMedCrossRef
13.
go back to reference Brandauer B, Hermsdörfer J, Beck A, Aurich V, Gizewski ER, Marquardt C, Timmann D (2008) Impairments of prehension kinematics and grasping faces in patients with cerebellar degeneration and the relationship to cerebellar atrophy. Clin Neurophysiol (in press) Brandauer B, Hermsdörfer J, Beck A, Aurich V, Gizewski ER, Marquardt C, Timmann D (2008) Impairments of prehension kinematics and grasping faces in patients with cerebellar degeneration and the relationship to cerebellar atrophy. Clin Neurophysiol (in press)
14.
go back to reference Thach WT, Kane SA, Mink JW, Goodkin HP (1992) Cerebellar output, multiple maps and modes of control in movement coordination. In: Llinas R, Sotelo C (eds) The cerebellum revisited. Springer, New York, pp 283–300 Thach WT, Kane SA, Mink JW, Goodkin HP (1992) Cerebellar output, multiple maps and modes of control in movement coordination. In: Llinas R, Sotelo C (eds) The cerebellum revisited. Springer, New York, pp 283–300
15.
go back to reference Urban PP, Marx J, Hunsche S, Gawehn J, Vucurevic G, Wicht S, Massinger C, Stoeter P, Hopf HC (2003) Cerebellar speech representation: lesion topography in dysarthria as derived from cerebellar ischemia and functional magnetic resonance imaging. Arch Neurol 60:965–972PubMedCrossRef Urban PP, Marx J, Hunsche S, Gawehn J, Vucurevic G, Wicht S, Massinger C, Stoeter P, Hopf HC (2003) Cerebellar speech representation: lesion topography in dysarthria as derived from cerebellar ischemia and functional magnetic resonance imaging. Arch Neurol 60:965–972PubMedCrossRef
17.
go back to reference Konczak J, Schoch B, Dimitrova A, Gizewski E, Timmann D (2005) Functional recovery of children and adolescents after cerebellar tumour resection. Brain 128:1428–1441PubMedCrossRef Konczak J, Schoch B, Dimitrova A, Gizewski E, Timmann D (2005) Functional recovery of children and adolescents after cerebellar tumour resection. Brain 128:1428–1441PubMedCrossRef
18.
go back to reference Ilg W, Giese MA, Gizewski ER, Schoch B, Timmann D (2008) The influence of focal cerebellar lesions on the control and adaptation of gait. Brain (in press) Ilg W, Giese MA, Gizewski ER, Schoch B, Timmann D (2008) The influence of focal cerebellar lesions on the control and adaptation of gait. Brain (in press)
19.
go back to reference Schoch B, Dimitrova A, Gizewski ER, Timmann D (2006) Functional localization in the human cerebellum based on voxelwise statistical analysis: a study of 90 patients. Neuroimage 30:36–51PubMedCrossRef Schoch B, Dimitrova A, Gizewski ER, Timmann D (2006) Functional localization in the human cerebellum based on voxelwise statistical analysis: a study of 90 patients. Neuroimage 30:36–51PubMedCrossRef
20.
go back to reference Grodd W, Hülsmann E, Lotze M, Wildgruber D, Erb M (2001) Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization. Hum Brain Mapp 13:55–57PubMedCrossRef Grodd W, Hülsmann E, Lotze M, Wildgruber D, Erb M (2001) Sensorimotor mapping of the human cerebellum: fMRI evidence of somatotopic organization. Hum Brain Mapp 13:55–57PubMedCrossRef
21.
go back to reference Eckmiller R, Westheimer G (1983) Compensation of oculomotor deficits in monkeys with neonatal cerebellar ablations. Exp Brain Res 49:315–326PubMedCrossRef Eckmiller R, Westheimer G (1983) Compensation of oculomotor deficits in monkeys with neonatal cerebellar ablations. Exp Brain Res 49:315–326PubMedCrossRef
22.
go back to reference Gerwig M, Kolb FP, Timmann D (2007) The involvement of the human cerebellum in eyeblink conditioning. Invited review. Cerebellum 6:38–57PubMedCrossRef Gerwig M, Kolb FP, Timmann D (2007) The involvement of the human cerebellum in eyeblink conditioning. Invited review. Cerebellum 6:38–57PubMedCrossRef
23.
go back to reference Christian KM, Thompson RF (2003) Neural substrates of eyeblink conditioning: acquisition and retention. Learn Mem 10:427–455PubMedCrossRef Christian KM, Thompson RF (2003) Neural substrates of eyeblink conditioning: acquisition and retention. Learn Mem 10:427–455PubMedCrossRef
24.
go back to reference De Zeeuw CI, Yeo CH (2005) Time and tide in cerebellar memory formation. Curr Opin Neurobiol 15:667–667PubMedCrossRef De Zeeuw CI, Yeo CH (2005) Time and tide in cerebellar memory formation. Curr Opin Neurobiol 15:667–667PubMedCrossRef
25.
go back to reference Dimitrova A, Gerwig M, Brol B, Gizewski ER, Forsting M, Beck A, Aurich V, Kolb FP, Timmann D (2008) Correlation of cerebellar volume with eyeblink conditioning in healthy subjects and in patients with cerebellar cortical degeneration. Brain Res 1198:73–78PubMedCrossRef Dimitrova A, Gerwig M, Brol B, Gizewski ER, Forsting M, Beck A, Aurich V, Kolb FP, Timmann D (2008) Correlation of cerebellar volume with eyeblink conditioning in healthy subjects and in patients with cerebellar cortical degeneration. Brain Res 1198:73–78PubMedCrossRef
26.
go back to reference Gerwig M, Hajjar K, Dimitrova A, Maschke M, Kolb FP, Frings M, Thilmann AF, Forsting M, Diener HC, Timmann D (2005) Timing of conditioned eyeblink responses is impaired in cerebellar patients. J Neurosci 25:3919–3931PubMedCrossRef Gerwig M, Hajjar K, Dimitrova A, Maschke M, Kolb FP, Frings M, Thilmann AF, Forsting M, Diener HC, Timmann D (2005) Timing of conditioned eyeblink responses is impaired in cerebellar patients. J Neurosci 25:3919–3931PubMedCrossRef
27.
go back to reference Attwell PJ, Rahman S, Yeo CH (2001) Acquisition of eyeblink conditioning is critically dependent on normal function in cerebellar cortical lobule HVI. J Neurosci 21:5715–5722PubMed Attwell PJ, Rahman S, Yeo CH (2001) Acquisition of eyeblink conditioning is critically dependent on normal function in cerebellar cortical lobule HVI. J Neurosci 21:5715–5722PubMed
28.
go back to reference Perrett SP, Ruiz BP, Mauk MD (1993) Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci 13:1708–1718PubMed Perrett SP, Ruiz BP, Mauk MD (1993) Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses. J Neurosci 13:1708–1718PubMed
29.
go back to reference Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timmann D, Honnorat J, Nighoghossian N, Manyam B (1997) International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci 145:205–201PubMedCrossRef Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timmann D, Honnorat J, Nighoghossian N, Manyam B (1997) International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci 145:205–201PubMedCrossRef
30.
go back to reference Schmahmann JD, Doyon J, Toga AW, Petrides M, Evans AC (2000) MRI atlas of the human cerebellum. Academic Press, San Diego Schmahmann JD, Doyon J, Toga AW, Petrides M, Evans AC (2000) MRI atlas of the human cerebellum. Academic Press, San Diego
Metadata
Title
Lesion-Symptom Mapping of the Human Cerebellum
Authors
D. Timmann
B. Brandauer
J. Hermsdörfer
W. Ilg
J. Konczak
M. Gerwig
E. R. Gizewski
B. Schoch
Publication date
01-12-2008
Publisher
Springer-Verlag
Published in
The Cerebellum / Issue 4/2008
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-008-0066-4

Other articles of this Issue 4/2008

The Cerebellum 4/2008 Go to the issue