Biomedical subjects

D Timmann

Publications and source records attributed to D Timmann.

At least 19 recordsLinked to original sources

PubMed2006

Comparison of the electrically evoked leg withdrawal reflex in cerebellar patients and healthy controls.

The aim of this study was to analyze the contribution of the cerebellum in the performance of the lower limb withdrawal reflexes. This has been accomplished by comparing the electrically evoked responses in cerebellar patients (CBL) with those in sex- and age-matched healthy control subjects (CTRL). The stimulus was applied to the subjects' medial plantar nerve in four blocks of ten trials each with switching the stimulus from one leg to the other after each block. Responses of the main muscle groups (tibial muscle: TA; gastrocnemius muscle: GA; rectus femoris muscle: RF; biceps femoris muscle: BI) of both legs were recorded during each stimulus. The group of CBL patients consisted of both focally lesioned patients (CBLf) and patients presenting a diffuse degenerative pathology (CBLd). (1) For the withdrawal reflex in CTRL subjects, responses were observed in distal and proximal muscles of the ipsilateral side and corresponding concomitant responses on the side contralateral to the stimulation, whereas in CBL patients responses were restricted primarily to distal muscles, particularly the TA of the ipsilateral, i.e. the stimulated, side. (2) The sequence of activation of the different distal and proximal muscles ipsilateral to the stimulation, derived from latencies and times-to-peak, was for the CTRL group: TA-GA-BI-RF. This sequence was found also in the CBLf patients on their unaffected side. However, on their affected side CBLf patients showed very early GA activation, almost simultaneously with TA and RF activations and before BI activation. RF activation before BI activation was also found in CBLd. In the latter group, GA was activated after RF but before BI with all responses typically delayed. (3) The general pattern of the electrically evoked lower limb reflex consisted of an early, excitatory F1 component and a later, excitatory F2 component of larger amplitude observed in the CTRL subjects and the CBLd patients. In contrast to this pattern CBLf patients exhibited large F1 components followed by small F2 components. (4) The characteristic differences in the withdrawal reflex responses of cerebellar patients depended on the type of the lesion, providing evidence for an important involvement of the cerebellum in the control of the performance of withdrawal reflexes.

Action Potentials↗

PubMed2006

Activation of cerebellar nuclei comparing finger, foot and tongue movements as revealed by fMRI.

The aim of the present study was to compare possible activation of the interposed and dentate cerebellar nuclei during finger, foot and tongue movements using functional magnetic resonance imaging (fMRI). Nineteen healthy control subjects performed sequential finger and repetitive tongue and foot movement tasks. Thin slices (2.5mm) were acquired of the cerebellar region containing the cerebellar nuclei with high spatial resolution (matrix size 128 x 128 x 10) using a Siemens 1.5T Sonata system. Use of an eight channel head coil provided better signal-to-noise-ratio compared to standard head coils. Only data of those 12 subjects were included in final statistical analysis, who showed significant activation of the cerebellar nuclei at least in one task. Cortical activations of the superior cerebellum were found in accordance to the known somatotopy of the human cerebellar cortex. Nuclear activations were most significant in the sequential finger movement task. Both interposed nuclei and ipsilateral dentate nucleus were activated. Dentate activation was present in the more caudal parts of both the dorsal and ventral nucleus. Activation overlapped with motor and non-motor domains of the dentate nucleus described by Dum and Strick [R.P. Dum, P.L. Strick, An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex, J. Neurophysiol. 89 (2003) 634-639] based on anatomical data in monkey. Tongue movement related activations were less extensive and overlapped with activations of caudal parts of the dentate nucleus in the finger movement task. No nuclear activation was seen following foot movements. The present findings show that both interposed and dentate nuclei are involved in sequential finger movements in humans. Interposed nucleus likely contributes to movement performance. Although no direct conclusions could be drawn based on the present data, different parts of the dentate nucleus may contribute to movement performance, planning and possible non-motor parts of the task.

Adult↗

PubMed2006

Verb generation in children and adolescents with acute cerebellar lesions.

The aim of the present study was to examine verb generation in a larger group of children and adolescents with acute focal lesions of the cerebellum. Nine children and adolescents with cerebellar tumours participated. Subjects were tested a few days after tumour surgery. For comparison, a subgroup was tested also 1 or 2 days before surgery. None of the children had received radiation or chemotherapy at or before the time of testing. Eleven age- and education-matched control subjects participated. Subjects had to generate verbs to blocked presentations of photographs of objects. As control condition, the objects had to be named. Furthermore, dysarthria was quantified by means of a sentence production and syllable repetition task. Detailed analysis of individual 3D-MR images revealed that lesions affected cerebellar hemispheres in all children and adolescents. The right cerebellar hemisphere was affected in four and the left hemisphere in five subjects. In the present study, naming and verb generation accuracy were preserved in the majority of subjects with cerebellar lesions. No significant signs of learning deficits were observed, as reduction of reaction times over blocks was not different compared to controls. There was a trend of children and adolescents with right-hemispheric lesions to perform worse compared to controls. In this group, however, significant signs of dysarthria were present. In sum, no significant signs of disordered verb generation were observed in children and adolescents with acute cerebellar lesions. Findings suggest that the role of the cerebellum in verb generation may be less pronounced than previously suggested. Findings need to be confirmed in a larger group of subjects with acute focal lesions.

Acute Disease↗

PubMed2005

Trace eyeblink conditioning in human subjects with cerebellar lesions.

Trace eyeblink conditioning was investigated in 31 patients with focal cerebellar lesions and 19 age-matched controls. Twelve patients presented with lesions including the territory of the superior cerebellar artery (SCA). In 19 patients lesions were restricted to the territory of the posterior inferior cerebellar artery (PICA). A 3D magnetic resonance imaging was used to determine the extent of the cortical lesion and possible involvement of cerebellar nuclei. Eyeblink conditioning was performed using a 40 ms tone as conditioned stimulus (CS) followed by a stimulus free trace-interval of 400 ms and a 100 ms air-puff as unconditioned stimulus (US). In SCA patients with lesions including parts of the cerebellar interposed nucleus trace eyeblink conditioning was significantly impaired. Pure cortical lesions of the superior cerebellum were not sufficient to reduce acquisition of trace conditioned eyeblink responses. PICA patients were not impaired in trace eyeblink conditioning. Consistent with animal studies the findings of the present human lesion study suggest that, in addition to forebrain areas, the interposed nucleus is of importance in trace eyeblink conditioning. Although cortical cerebellar areas appear less important in trace compared with delay eyeblink conditioning, the present data strengthen the view that cerebellar structures contribute to different forms of eyeblink conditioning paradigms.

Adult↗

PubMed2005

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.

Adolescent↗

PubMed2005

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.

Adult↗

PubMed2005

Children and adolescents with chronic cerebellar lesions show no clinically relevant signs of aphasia or neglect.

We studied language and visuospatial functions of 12 children and adolescents who had undergone surgery for cerebellar astrocytoma without subsequent radiation or chemotherapy and compared them with 27 age-, gender-, and education-matched healthy control subjects. To study possible lateralization of the functions of the left and right cerebellar hemispheres, subjects performed several language tasks including a verb-generation task as well as standard neglect and extinction tests. Three-dimensional-MR images confirmed that lesions affected cerebellar hemispheres in all children but one who had a pure vermal lesion. The right cerebellar hemisphere was affected in six, the left hemisphere in four children, and both hemispheres in one child. There were no signs of aphasia in the children or adolescents with cerebellar lesions. Language abilities did not differ between cerebellar patients and control subjects except for small increases in reaction times in verb generation in patients with left-sided lesions. Visuospatial functions were also intact in cerebellar subjects except for minor group differences in neglect tasks. In sum, chronic focal cerebellar lesions acquired in childhood or youth do not result in persistent language disorders or clinically significant signs of spatial neglect or extinction.

Adolescent↗

PubMed2005

Incidence of dysarthria in children with cerebellar tumors: a prospective study.

The present study investigated dysarthric symptoms in children with cerebellar tumors. Ten children with cerebellar tumors and 10 orthopedic control children were tested prior and one week after surgery. Clinical dysarthric symptoms were quantified in spontaneous speech. Syllable durations were analyzed in syllable repetition and sentence production tasks. Localization of the cerebellar lesions were defined after manual transfer from individual 2D-MR images onto 3D images of a spatially normalized healthy brain. Cerebellar children showed few and mild clinical signs of dysarthria. No difference was present in the sentence production task compared to controls. In five cerebellar children, syllables were prolonged in the syllable repetition task after surgery. Syllable duration normalized in an additional four-week session in all but one case. The MR-analysis showed that superior paravermal cerebellar areas likely involved in dysarthria in adults (paravermal lobules HVI, Crus I) were not significantly affected. In children, speech impairments appear to be rare after cerebellar surgery because tumors most commonly affect posterior-inferior and medial parts of the cerebellum while critical cerebellar regions are likely spared. The results suggest a similar localization of speech functions in the cerebellum in children and adults.

Acoustic Stimulation↗

PubMed2005

Cerebellar agenesis II: motor and language functions.

In a former study of a patient with cerebellar agenesis (HK) mild motor deficits, problems in delay eyeblink conditioning and mild to moderate deficits in IQ, planning behavior, visuospatial abilities, visual memory, and attention were found. The present study reports additional findings in the same patient. In the motor domain, impairments in fine motor manipulations, trace eyeblink conditioning and motor imagination in a functional magnetic resonance (fMRI) study were found. Based on fMRI findings; however, cortical areas involved in a tapping task did not significantly differ from a healthy control group. In the cognitive domain, deficits in speech comprehension as well as verbal learning and declarative memory were present. No significant affective symptoms were observed. Although problems in executive, visuospatial and language tasks are in agreement with the so-called cerebellar cognitive affective syndrome-other possibilities remain. Non-motor impairments in HK might also be a consequence of lacking motor abilities in development and motor deficits may interfere with the performance of parts of the cognitive tasks. In addition, lack of promotion and learning opportunities in childhood may contribute and mental retardation based on extracerebellar dysfunction cannot be excluded.

Affect↗

PubMed2004

Eyeblink conditioning in patients with hereditary ataxia: a one-year follow-up study.

Delay eyeblink conditioning was examined in patients with genetically-defined heredoataxias and age-matched control subjects. 24 patients with spinocerebellar ataxia type 6 (SCA6), type 3 (SCA3), and Friedreich's ataxia (FRDA) participated. SCA6 affects primarily the cerebellum, whereas extracerebellar involvement is common in SCA3 and FRDA. Testing was performed in three sessions six months apart. Severity of ataxia was defined based on the International Ataxia Cooperative Rating Scale (ICARS). As expected, cerebellar patients were significantly impaired in eyeblink conditioning compared to controls. Signs of retention and further learning across sessions were present in controls, but not in the cerebellar patients. In addition, findings of disturbed timing of conditioned responses were observed. Both onsets and peaks of the conditioned responses (CRs) occurred significantly earlier in cerebellar patients. Shortened CR responses were most prominent in patients with primarily cerebellar cortical disease (SCA6). In the group of all cerebellar patients, the SCA3 and the FRDA group correlations between learning deficits and clinical findings were weak. Moderate-to-strong correlations were found in the SCA6 patients. There was no significant change, however, in clinical ataxia scores and CR incidence across the three sessions. In summary, impaired learning of conditioned eyeblink responses is a stable finding across multiple sessions in patients with degenerative cerebellar disorders. Eyeblink conditioning may be a useful measure of cerebellar impairment in patients with hereditary ataxias that primarily affect the cerebellum (such as SCA6). In other heredoataxias (such as SCA3 and FRDA), extracerebellar involvement not assessed by ICARS likely contributes to eyeblink conditioning abnormalities.

Adult↗

PubMed2004

Stimulus-response versus stimulus-stimulus-response learning in cerebellar patients.

Ample evidence exists that the cerebellum is involved in associative motor learning, particularly in eyeblink-conditioning. In visuomotor associative learning the role of the cerebellum is less clear. One open question is whether cerebellar patients' deficits in visuomotor learning are present both in a stimulus-response and a stimulus-stimulus-response association task. Twelve patients with cerebellar degeneration and 12 healthy matched control subjects participated. A magnetic resonance imaging (MRI) volumetric analysis of the cerebellum was performed to assess the degree of cerebellar atrophy. In a blocked design, subjects had to learn the association between one color square or two color squares and a right or left key press. In the latter condition, the two colors were shown one after the other in the same sequence except for two blocks at the end of the experiment. Overall, cerebellar subjects reacted significantly slower than controls. In both groups, reaction time decreased over blocks, and the learning effect was more pronounced in the stimulus-response than in the stimulus-stimulus-response condition. Post hoc analyses revealed that learning differences between conditions were significant in cerebellar patients but not control subjects. Furthermore, only healthy subjects were irritated, i.e., they significantly increased reaction times in the blocks with reversed sequence in the stimulus-stimulus-response condition. Cerebellar subjects tended to name less correct stimulus-stimulus-response associations after the experiment. Finally, cerebellar volume correlated with parameters of motor performance, but not learning. In conclusion, cerebellar patients showed deficits in stimulus-stimulus-response, but not stimulus-response learning. Future experiments are needed to differentiate between possible deficits in learning the stimulus-stimulus association, use of sequence information, and/or impaired motor performance interfering with learning.

Adult↗

PubMed2004

Classically conditioned postural reflex in cerebellar patients.

The aim of the current study was to compare postural responses to repetitive platform-evoked perturbations in cerebellar patients with those of healthy subjects using a classical conditioning paradigm. The perturbations consisted of tilting of the platform (unconditioned stimulus: US) at random time intervals, preceded by an auditory signal that represented the conditioning stimulus (CS). Physiological reactions were recorded biomechanically by measuring the vertical ground forces, yielding the center of vertical pressure (CVP), and electrophysiologically by EMG measurements of the main muscle groups of both legs. The recording session consisted of a control section with US-alone trials, a testing section with paired stimuli and a brief final section with US-alone trials. Healthy control subjects were divided into those establishing conditioned responses (CR) in all muscles tested (strategy I) and those with CR in the gastrocnemius muscles only (strategy II), suggesting an associative motor-related process is involved. Patients with a diffuse, non-localized disease were almost unable to establish CR. This was also true for a patient with a focal surgical lesion with no CR on the affected side but who, simultaneously, showed an essentially normal CR incidence on the intact side. During US-alone trials healthy controls exhibited a remarkable decay of the UR amplitude due to a non-associative motor-related process such as habituation. The decay was most prominent in the paired trials section. In contrast, patients showed no significant differences in the UR amplitude throughout the entire recording session. Analysis of the CVP supported the electrophysiological findings, showing CR in the controls only. The differences between the responses of control subjects and those of the cerebellar patients imply strongly that the cerebellum is involved critically in controlling associative and non-associative motor-related processes.

Adult↗

PubMed2004

Do children with focal cerebellar lesions show deficits in shifting attention?

More recent findings suggest a possible role of the cerebellum in nonmotor functions. Disability of individuals with cerebellar damage in rapidly shifting attention is one frequently used example to support cerebellar involvement in mental skills. The original proposal was based on findings in five children with chronic surgical lesions of the cerebellum and a young adult with a degenerative disorder. The aim of the present study was to repeat Akshoomoff and Courchesne's initial findings in a larger group of children with focal cerebellar lesions. Ten children with cerebellar lesions and 10 age- and sex-matched controls were tested. Neocerebellar areas were affected in all children with cerebellar damage except one based on detailed analysis of MRI scans. Subjects had to perform a focus and a shift attention task. Two visual and two auditory stimuli were presented in a pseudorandom order. An ellipse and a high-pitched tone were presented less frequently than a circle and a low-pitched tone. Rare stimuli were presented at five different time intervals. In the focus tasks, subjects had to react to the same rare stimulus of one of the two modalities. In the shift task, subjects had to switch between the two rare stimuli. Motor deficits based on reaction times were small in cerebellar children compared with controls. The ability of target detection did not significantly differ in the children with cerebellar lesions compared with the control children in both the focus and the shift attention task. In particular, children with cerebellar damage showed no significant impairment in rapid (<2 s) shifts of attention. The present findings indicate that the cerebellum may be less critical in attention related processes than suggested previously.

Adolescent↗

PubMed2004

Amplitude changes of unconditioned eyeblink responses in patients with cerebellar lesions.

Timing and amplitude parameters of unconditioned eyeblink responses were investigated in 24 patients with unilateral cerebellar lesions following infarcts within the territory of the superior cerebellar artery (SCA, n=12) and of the posterior inferior cerebellar artery (PICA, n=12). The extent of cortical cerebellar lesions, i.e., which lobules were affected and possible involvement of cerebellar nuclei, was determined by three-dimensional magnetic resonance imaging (3D MRI). Amplitude parameters of eyeblink responses were normalized and expressed as percentage of the unaffected side in patients and the second tested side in age-matched controls. Normalized peak amplitudes, burst area and burst duration were significantly increased in SCA patients with lesions restricted to cortical areas. Burst onset and time to peak were not significantly different compared with controls. Temporal and amplitude parameters of eyeblink responses were unchanged in SCA patients with additional involvement of cerebellar nuclei and in patients with lesions of the PICA territory. Consistent with animal lesion and recording studies and a recent human functional magnetic resonance imaging (fMRI) study, the present data suggest that cortical areas of the superior cerebellum are of importance in eyeblink control in humans. These areas partly overlap with areas known to be critical in eyeblink conditioning.

Adult↗

PubMed2004

Cerebellar mutism--report of four cases.

The aim of the present study was to investigate the manifestations of mutism after surgery in children with cerebellar tumors. Speech impairment following cerebellar mutism in children was investigated based on standardized acoustic speech parameters and perceptual criteria. Mutistic and non-mutistic children after cerebellar surgery as well as orthopedic controls were tested pre-and postoperatively. Speech impairment was compared with the localization of cerebellar lesions (i. e. affected lobules and nuclei). Whereas both control groups showed no abnormalities in speech and behavior, the mutistic group could be divided into children with dysarthria in post mutistic phase and children with mainly behavioral disturbances. In the mutistic children involvement of dentate and fastigial nuclei tended to be more frequent and extended than in the nonmutistic cerebellar children. Cerebellar mutism is a complex phenomenon of at least two types. Dysarthric symptoms during resolution of mutism support the anarthria hypothesis, while mainly behavioral changes suggest an explanation independent from speech motor control.

Age Factors↗

PubMed2004

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.

Adult↗

PubMed2004

[Tetanus in cats: 3 case descriptions].

Three cats with spasticity on one leg or on all four limbs were presented between 1996 and 1998 at the Department of clinical veterinary medicine, Section of neurology, Vetsuisse-Faculty of Bern. The presumptive diagnosis was tetanus. A focal form was present in two cases and generalised tetanus in one cat. All cats had a history of injury at the affected legs respectively at the neck. The first clinical signs were seen between two days and three weeks after injury. The bacteriologic examination of serous fluid from the site of injury revealed an infection with Clostridium. EMG in one cat during anaesthesia showed motor united potentials (MUPs) on the spastic leg. All patients received antibiotics (Penicillin, respectively Amoxicillin/Clavulanic acid and Metronidazol). Supportive aid were initially sedation, wound revision and in one cat nutrition through oesophageal sonde. In a second phase physiotherapy was performed. All three animals were significantly better after a couple of weeks, two cats were without symptoms after eight and five weeks respectively.

Animals↗

PubMed2004

Use of sequence information in associative learning in control subjects and cerebellar patients.

Previous studies of our group have shown that cerebellar patients are impaired in their ability to associate a color and a numeral or two colors with a button push. The aim of the present study was to examine whether control subjects make use of sequence information in visuomotor associative learning tasks and if this ability is impaired in cerebellar patients. A group of eight patients with degenerative cerebellar disease and eight age, sex and IQ matched controls were tested. Subjects had to learn the association between pairs of colored squares and a button push. Two colored squares were shown one after the other in a fixed or random order on a computer screen. Control subjects but not cerebellar patients took advantage of the fixed order information of colored squares in order to improve associative learning. Differences between groups could not be explained by differences in verbal and visuospatial short-term memory, color discrimination, affective state or motor disturbances. Results suggest that impaired sequencing of sensory stimuli may contribute to disorders in visuomotor associative learning in cerebellar patients.

Adult↗