A. Dimitrova

Functional localization in the human cerebellum based on voxelwise statistical analysis: a study of 90 patients.

The aim of the present study was to examine somatotopy in the cerebellar cortex and a possible differential role of the cerebellar cortex and nuclei in functional outcome. Clinical findings and 3D MRI-based cerebellar lesions site were compared in a group of 90 patients with focal cerebellar lesion using International Cooperative Ataxia Rating Scale (ICARS) and voxel-based lesion-symptom mapping (VLSM). Separate analysis was performed in patients with acute and chronic ischemic lesions (n=43) and patients with acute and chronic surgical lesions (n=47). Thirty-eight patients were included after resection of a cerebellar tumor in childhood or adolescence. The most significant lesion symptom correlations were observed in the subgroup with acute ischemic lesions. Limb ataxia was significantly correlated with lesions of the interposed (NI) and part of the dentate nuclei (ND), ataxia of posture and gait with lesions of the fastigial nuclei (NF) including NI. Correlations with cortical lesions were less significant and present in the superior cerebellum only. Upper limb ataxia was correlated with lesions of vermal, paravermal and hemispheral lobules IV-V and VI, lower limb ataxia with lesions of vermal, paravermal and hemispheral lobules III and VI, dysarthria with lesions of paravermal and hemispheral lobules V and VI and ataxia of posture and gait with lesions of vermal and paravermal lobules II, III and IV. In the subgroups with chronic focal lesions, similar correlations were observed with lesions of the cerebellar nuclei, but significantly less correlations with lesions of the cerebellar cortex. Functional localization based on VLSM backs findings in previous animal and functional brain images studies in healthy human subjects. The lesion site appears to be critical for motor recovery. Lesions affecting the cerebellar nuclei are not fully compensated at any age and independent of the pathology in humans.

MRI atlas of the human cerebellar nuclei.

The differential role of the cerebellar cortex and nuclei has rarely been addressed in human lesion and functional brain imaging studies. One important reason is the difficulty of defining the localization of the cerebellar nuclei and extent of possible lesions based on CT or MR scans. The present MRI investigation was specifically designed to study the anatomy of the deep cerebellar nuclei. In both basal ganglia and cerebellar nuclei of healthy human subjects the amount of iron is high compared to the rest of the brain. Clusters of iron are paramagnetic and, therefore, tend to cause local inhomogenities in a magnetic field. The iron-induced susceptibility artefacts were used to visualize the cerebellar nuclei as hypointensities on MR images. A three-dimensional atlas of the dentate (D), interposed (I), and fastigial (F) nuclei is presented in standard proportional stereotaxic space coordinates based on findings in a healthy 26-year-old female. A three-dimensional axial volume of the cerebellum was acquired using a T1-weighted fast low-angle shot (FLASH) sequence on a Siemens Sonata 1.5 Tesla MR. To increase the signal to noise ratio the sequence was acquired 5 times and averaged. Each volume was registered, resampled to 1.00 x 1.00 x 1.00-mm3 voxel size and spatially normalized into a standard proportional stereotaxic space (the MNI-space) using SPM99. Localization of cerebellar nuclei were confirmed by comparison with postmortem MRI and histological microsections of another brain.

Timing of Conditioned Eyeblink Responses Is Impaired in Cerebellar Patients

In the present study, timing of conditioned eyeblink responses (CRs) was investigated in cerebellar patients and age-matched controls using a standard delay paradigm. Findings were compared with previously published data of CR incidences in the same patient population (Gerwig et al., 2003; Timmann et al., 2005). Sixteen patients with pure cortical cerebellar degeneration (spinocerebellar ataxia type 6 and idiopathic cerebellar ataxia), 14 patients with lesions within the territory of the superior cerebellar artery, and 13 patients with infarctions within the territory of the posterior inferior cerebellar artery were included. The affected cerebellar lobules and possible involvement of cerebellar nuclei were determined by three-dimensional magnetic resonance imaging (MRI) in patients with focal lesions (n = 27). Based on a voxel-by-voxel analysis, MRI lesion data were related to eyeblink conditioning data. CR incidence was significantly reduced, and CRs occurred significantly earlier in patients with cortical cerebellar degeneration and lesions of the superior cerebellum compared with controls. Incidence and timing of CRs was not impaired in patients with lesions restricted to the posterior and inferior cerebellum. Voxel-based MRI analysis revealed that cortical areas within the anterior lobe (Larsell lobule HV) were most significantly related to timing deficits, whereas reduced CR incidences were related to more caudal parts (lobule HVI) of the superior cerebellar cortex. The present data suggest that different parts of the superior cerebellar cortex may be involved in the formation of the stimulus association and appropriate timing of conditioned eyeblink responses in humans. Extracerebellar premotoneuronal disinhibition, however, is another possible explanation for changes in CR timing.

Cerebellar involvement in verb generation: an fMRI study.

A possible role of the human cerebellum in the generation of verbs corresponding to presented nouns has been suggested. Previous functional brain imaging studies have compared generation of verbs with the reading of nouns as a measure of verb generation. In the present fMRI study involving healthy human subjects, the effects of speech articulation and motor imagery associated with verb production were investigated in greater detail. Generation of verbs to visually presented nouns was compared to a condition in which subjects read those same verbs that had been individually generated by each subject. Activation in lobule HVI/Crus I of the right cerebellar hemisphere was found as a measure of verb generation. In contrast, reading of verbs as a measure of speech articulation evoked cerebellar activations in both left and right paravermal lobule VI. These results suggest an involvement of the right lateral cerebellar hemisphere in linguistic functions during verb generation. Alternatively, effects of inner speech could also possibly explain the results.

Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei.

In a previous study, a three-dimensional (3D) MRI atlas of the human cerebellar nuclei was introduced based on findings in one healthy human subject [Dimitrova, A., Weber, J., Redies, C., Kindsvater, K., Maschke, M., Kolb, F.P., Forsting, M., Diener, H.C., Timmann, D., 2002. MRI atlas of the human cerebellar nuclei. NeuroImage 17, 240-255]. The present MRI investigation was designed to study variability of the anatomy of the dentate/interposed nuclei in a larger group of healthy subjects. Similar to our previous study, iron-induced susceptibility artifacts were used to visualize the cerebellar nuclei as hypointensities on MR images. Data of 63 healthy subjects (27 female, 36 male; mean age 45.3+/-13.4 years, age range 22--71 years) were included. A 3D axial volume of the cerebellum was acquired using a T2*-weighted FLASH sequence on a Siemens Sonata 1.5 T MR scanner. Each volume was registered, re-sampled to 1.00 x 1.00 x 1.00 mm(3) voxel size and spatially normalized into a standard proportional stereotaxic space using SPM99. Dentate/interposed nuclei were traced on axial images and saved as regions of interest using MRIcro-software by two independent examiners. A probabilistic 3D MRI atlas of the cerebellar dentate/interposed nuclei is presented based on findings in all subjects.

Cognitive functions in patients with MR-defined chronic focal cerebellar lesions.

The aim of the present study was to examine cognitive functions in a group of chronic patients with focal cerebellar lesions. Both effects of localization (anterior vs. posterior lobe) and side (left vs. right cerebellar hemisphere) were of interest. Fourteen patients with infarctions within the territory of the posterior inferior cerebellar artery (PICA) and seven patients with infarctions within the territory of the superior cerebellar artery (SCA) participated. The affected lobules and nuclei were assessed based on 3D MR imaging. The right cerebellar hemisphere was affected in eight PICA and two SCA patients, the left hemisphere in six PICA and four SCA patients. One SCA patient revealed a bilateral lesion. In order to study possible lateralization of functions, subjects performed a language task as well as standard neglect and extinction tests. Moreover, two tests of executive functions were applied. There were no significant group differences apart from a verbal fluency task, in which all cerebellar patients - but especially those with right-sided lesions - were impaired. Voxel-based lesionsymptom mapping (VLSM) revealed that a lesion of the right hemispheric lobule Crus II was associated with impaired performance in the verbal fluency task. In sum, the results showed preserved cognitive abilities in chronic cerebellar patients apart from impairments of verbal fluency in patients with right-cerebellar lesions. The latter findings are in line with the assumption that the right posterolateral cerebellar hemisphere supports functions associated with verbal fluency.

Brain Representation of Hemifield Stimulation in Poststroke Visual Field Defects

Background and Purpose— Plasticity in extended, parallel, or reciprocal operating networks is well recognized. Changes in neuronal activity after lesions to distinct localized structures, such as the primary visual cortex, are less well characterized. We investigated the cortical reorganization in patients with poststroke visual field defects using blood oxygen level–dependent functional MRI. Methods— Brain activation was measured in 7 patients with a single occipital cortical lesion and partially recovered hemianopia and in 7 age-matched control subjects. Differences in activation between rest and visual hemifield stimulation were assessed with statistical parametric mapping (SPM’99). Results— In normal subjects, significant activation was found in the contralateral primary visual cortex and bilaterally in the extrastriate cortex. During hemifield stimulation of the unaffected side of stroke patients, a similar pattern was found compared with that seen in control subjects. During stimulation of the hemianopic side, bilateral activation was seen within the extrastriate cortex, stronger in the ipsilateral hemisphere. The primary visual cortex was not significantly activated in either hemisphere during stimulation of the hemianopic side. Conclusions— Visual field defects after stroke are associated with bilateral activation of the extrastriate visual cortex. This pattern of activation indicates altered neuronal activity in the visual system. Further investigation is necessary to determine the relationship between functional reorganization and recovery of lost visual function after poststroke hemianopia.

Preserved verb generation in patients with cerebellar atrophy.

A role of the right cerebellar hemisphere has been suggested in linguistic functions. Nevertheless, studies of verb generation in cerebellar patients provide inconsistent results. The aim of the present study was to examine verb generation in a larger group of cerebellar patients with well-defined lesions. Ten subjects with degenerative cerebellar disorders and ten healthy matched controls participated. Subjects had to generate verbs to the blocked presentation of photographs of objects (i.e. four blocks of sixteen objects). As control condition, the objects had to be named. Furthermore, dysarthria was quantified by means of a sentence production and syllable repetition task. Volumetric analysis of individual 3D-MR scans was performed to quantify cerebellar atrophy. Cerebellar patients were slower in the sentence production and syllable repetition tasks, and cerebellar volume was decreased compared to controls. Despite cerebellar atrophy and dysarthria, the answers produced did not differ between patients and controls. In addition, both groups revealed the same amount of decrease in verbal reaction time over blocks (i.e. learning). The results suggest that the role of the cerebellum in verb generation is less pronounced than previously suggested.

Behavioral and affective changes in children and adolescents with chronic cerebellar lesions.

The aim of the present study was to investigate if clinically relevant affective or behavioral changes as described in adults in the cerebellar affective syndrome by Schmahmann and Sherman [The cerebellar cognitive affective syndrome, Brain 121 (1998) 561-579] are likely to occur as a long-term sequelae of cerebellar vermis lesions in children. Site and extent of the vermal lesion were defined on the basis of individual 3D-MRI scans and lesion data were correlated with behavioral and affective changes. Affect and behavior were assessed in children after cerebellar tumor surgery by means of experimenter ratings based on the description of the cerebellar affective syndrome and free ratings by the patients and their parents. Twelve children and adolescents with a former cerebellar astrocytoma surgery without subsequent radiation or chemotherapy participated. Detailed analysis of individual 3D-MR images revealed that lesions affected the vermis in nine children. Experimenter ratings according to Schmahmann revealed no relevant problems in patients. In five out of nine patients with vermal affection somewhat increased thoughtful, anxious or aggressive behavior was reported by patients and parents. In conclusion, minor behavioral and affective changes were present in a subset of children with chronic vermal lesions.

Degree of Cerebellar Ataxia Correlates with Three-Dimensional MRI-Based Cerebellar Volume in Pure Cerebellar Degeneration

The aim of the present study was to compare the severity of cerebellar ataxia as measured by the International Cooperative Ataxia Rating Scale (ICARS) by Trouillas et al. [ J Neurol Sci 1997;145:205–211] with the cerebellar volume in chronic cerebellar disease. Fifteen patients with pure cerebellar degeneration were investigated. Seven patients suffered from spinocerebellar ataxia type 6, 5 from idiopathic late-onset cerebellar ataxia, 2 from autosomal dominant cerebellar ataxia type III and 1 from episodic ataxia type 2. Volumetric analysis was based on individual three-dimensional MR images. Total ICARS score significantly inversely correlated with the cerebellar volume (r = –0.805, p < 0.0001), correlations between ICARS subscores and cerebellar volume were significant for upper and lower limb ataxia, ataxia of posture and gait, and dysarthria, but not for the oculomotor subscore. The results suggest that the degree of cerebellar atrophy in pure cerebellar degenerative disorders is accompanied by comparable functional impairment (i.e. degree of cerebellar ataxia).