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Biomedical subjects

D Timmann

Publications and source records attributed to D Timmann.

At least 37 records · Page 2Linked to original sources
PubMed2003

Overarm throwing speed in cerebellar subjects: effect of timing of ball release.

Cerebellar subjects cannot throw fast and show variability in ball speed from throw to throw. One possible reason is that they release the ball at times when arm speed is not at its maximal value. Therefore, we investigated the hypothesis that the slow and variable speeds of throws made by cerebellar subjects are caused by their known large variability in the timing of ball release. Eight cerebellar subjects and matched controls were instructed to make overarm throws fast and accurately. Angular positions of arm segments were recorded with search coils at 1,000 Hz. Timing of ball release was measured with respect to the time of occurrence of seven arm kinematic reference points. All cerebellar subjects showed strong relations between ball speed and the timing of ball release, with faster ball speeds associated with late ball release. In agreement, faster ball speeds were also associated with longer hand paths to ball release, and with balls which went low on the target. However, when timing of ball release was optimal for achieving maximal ball speed in the cerebellar subjects, their fastest ball speeds were on average only 67% those of controls. Similarly, peak forearm angular velocity (one measure of arm speed) in the cerebellar group was 58% that of the control group. It is concluded that the large variability in timing ball release in cerebellar subjects contributes to their variability in ball speed, but is only a minor factor in their inability to throw fast. The major reason why cerebellar subjects do not throw fast is that they do not generate fast arm speeds.

Adolescent↗
PubMed2003

Cerebellar responses evoked by nociceptive leg withdrawal reflex as revealed by event-related FMRI.

The aim of the present study was to examine nociceptive leg withdrawal reflex-related areas in the human cerebellum using event-related functional brain imaging (fMRI). Knowledge about cerebellar areas involved in unconditioned limb withdrawal reflex control has some relevance in understanding data of limb withdrawal reflex conditioning studies. Sixteen healthy adult subjects participated. Nociceptive leg withdrawal reflexes were evoked by electrical stimulation of the left tibial nerve behind the medial malleolus. An event-related fMRI paradigm was applied with a total of 30 stimuli being delivered pseudorandomly during 500 consecutive MR scans. Surface electromyographic (EMG) recordings were performed from the left anterior tibial muscle. Only trials with significant reflex EMG activity were used as active events in fMRI statistical analysis. The specified contrasts compared the active event condition with rest. Leg withdrawal reflex-related areas were located within the vermis, paravermis, and lateral posterior cerebellar hemispheres bilaterally. Vermal and paravermal areas in lobules III/IV in the anterior lobe and in lobule VIII in the posterior lobe agree with the cerebellar representation of climbing and mossy fiber hindlimb afferents and voluntary leg movements. They are likely related to efferent modulation of the leg withdrawal reflex and/or sensory processing of afferent inputs from the reflex and/or the noxious stimulus. Additional activation within vermal lobule VI and hemispheral lobules VI/Crus I may be related to other pain-related processes (e.g., facial grimacing, fear, and startlelike reactions).

Adult↗
PubMed2003

Cerebellar agenesis: clinical, neuropsychological and MR findings.

Cases of cerebellar agenesis are rare. The degree of motor impairment is a matter of discussion. It has been claimed that normal motor function can be observed. Detailed descriptions of neurological findings, however, are lacking. Neuropsychological testing in cerebellar agenesis is of additional interest based on recent findings of impaired non-motor functions in cerebellar disease. The case of an elderly woman with cerebellar agenesis is presented. 3D-MR imaging was used to confirm the diagnosis. Neurological and neuropsychological examination was performed including video documentation (see the authors' own website). To assess deficits of motor learning eyeblink conditioning was investigated. Neurological examination revealed mild to moderate signs of cerebellar dysarthria, upper and lower limb ataxia and ataxia of stance and gait. Motor learning was affected as shown by inability to acquire conditioned eyeblink responses. In addition, neuropsychological testing disclosed mild to moderate deficits in IQ, planning behavior, visuospatial abilities, memory and attention. Cerebellar ataxia, although clearly present, was less than one would expect in almost complete absence of the cerebellum. Neuropsychological deficits, on the other hand, appeared to be more marked than one would expect in cerebellar disease. No conclusion, however, could be drawn whether impaired cognitive development and neuropsychological test performance were directly related to lack of cerebellar function, or caused by impaired motor development and performance.

Ataxia↗
PubMed2003

Comparison of eyeblink conditioning in patients with superior and posterior inferior cerebellar lesions.

The aim of the present study was to compare eyeblink conditioning in cerebellar patients with lesions including the territory of the superior cerebellar artery (SCA) and in patients with lesions restricted to the territory of the posterior inferior cerebellar artery (PICA). The cerebellar areas known to be most critical in eyeblink conditioning based on animal data (i.e. Larsell lobule H VI and interposed nucleus) are commonly supplied by the SCA. Eyeblink conditioning was expected to be impaired in SCA, but not in PICA patients. A total of 27 cerebellar patients and 25 age-matched controls were tested. Cerebellar lesions were primarily unilateral (n = 20). Most patients suffered from ischaemic infarctions of the SCA (n = 11) or the PICA (n = 13). The other patients presented with cerebellar tumours (n = 2) and cerebellar agenesis (n = 1). The extent of the cortical lesion (i.e. which lobuli were affected) and possible involvement of the cerebellar nuclei was determined by 3D-MRI. As expected, the ability to acquire classically conditioned eyeblink responses was significantly reduced in the group of all cerebellar patients compared with the controls. In the patients with unilateral cerebellar lesions, conditioning deficits were present ipsilaterally. In SCA patients with lesions including hemispheral lobules VI and Crus I, eyeblink conditioning was significantly reduced on the affected side compared with the unaffected side. No significant difference between the affected and unaffected sides was present in patients with lesions restricted to the common PICA territory (i.e. Crus II and below). Conditioning deficits were neither significantly different in SCA patients with pure cortical lesions compared with SCA patients with additional nuclear impairment nor in SCA patients with unilateral lesions compared with SCA patients with bilateral lesions. To summarize, unilateral cortical lesions of the superior cerebellum appear to be sufficient to reduce eyeblink conditioning in humans significantly.

Adult↗
PubMed2002

Classical conditioning of postural reflexes.

Unexpected external perturbations of body equilibrium elicit compensatory postural reflexes. The reflex patterns change only minimally, even after repetitive perturbations. This study addressed the question of whether classical conditioning can alter the reflex patterns. In the first session 27 healthy subjects were tested when standing on an unexpectedly tilting platform. Electromyographic (EMG) activity from different leg muscles and the vertical ground forces, from which the centre of vertical pressure (CVP) was computed, were recorded. In a subsequent session subjects were tested using the classical conditioning paradigm with the tilting platform as the unconditioned stimulus (US) and a prior auditory signal as the conditioning stimulus (CS). The decay of the unconditioned response (UR) observed in the first session was similar and small in all subjects. During conditioning, 22% of the subjects established conditioned responses (CR) in all muscles recorded (strategy 1). UR amplitudes of the anterior tibialis (TA) decayed more than in the first session. The resulting CVP excursions were similar to those observed in US-alone trials. The remaining subjects exhibited CR only in the gastrocnemius muscle but developed a substantial decay of UR, resulting in very small CVP excursions (strategy 2). Our data suggest that processing of US-preceding conditioning stimulus leads to different strategies in the control of postural adjustment with assumed underlying associative and non-associative plastic processes.

Adult↗
PubMed2002

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.

Adult↗
PubMed2002

Disorders in timing and force of finger opening in overarm throws made by cerebellar subjects.

Although there is agreement that an important sign of cerebellar dysfunction is disorder in timing of movement, it appears that authors who study different behaviors mean different things when they use the term "timing," and that the underlying mechanisms are likely to be different. For overarm throwing, skilled throwers can time ball release with a precision of less than 7 ms, whereas cerebellar subjects show a large variability of 50 ms or more in this timing. Furthermore, cerebellar patients show a larger variability in the amplitude of finger opening which could either reflect a disorder in force, or result indirectly from the increased variability in timing. To determine whether timing and force of finger opening were dependent variables, the time of ball release was plotted against the amplitude of finger opening. In control subjects these two parameters were related, with early (mistimed) throws having smaller finger amplitudes. However, in cerebellar subjects the increased variability in finger amplitude could not be accounted for by the increased variability in timing. Similarly, the increased timing windows could not be explained by disorder in force at the fingers. It is concluded that the abnormal finger opening that occurs in cerebellar patients when making overarm throws results from increased variability in both the timing and force of finger extension. Whether the increased variability in timing is a disorder in triggering finger opening at the right moment, or is due to a failure to combine finger opening appropriately with the hand trajectory, remains to be determined.

Arm↗
PubMed2002

Fear conditioned changes of heart rate in patients with medial cerebellar lesions.

Fear conditioned changes of heart rate and skin conductance responses were investigated in patients with medial cerebellar lesions. A classical conditioning paradigm with a tone as the conditioned stimulus (CS) and an electrical shock as the unconditioned stimulus (US) was tested on five patients with medial cerebellar lesions due to surgery for astrocytoma and five controls. The CS preceded the US by 5900 ms and coterminated with the US. Changes in heart rate and skin conductance responses were obtained as measures for autonomic fear responses. Effects of conditioning were quantified by comparison of the habituation and extinction phases. Controls, but not cerebellar patients, showed a significant decrease of heart rate during fear conditioning. However, there were no significant fear conditioned changes in electrodermal responses in either group. In summary, the medial cerebellum seems to be involved in fear-conditioned bradycardia in humans.

Adolescent↗
PubMed2001

Perturbed step initiation in cerebellar subjects: 2. Modification of anticipatory postural adjustments.

Although ataxias of stance and gait are frequent manifestations of cerebellar disease, the number of human studies examining stance or gait in cerebellar subjects is limited. In the present study, we examined whether anticipatory postural adjustments were impaired in cerebellar subjects during perturbed and unperturbed step initiation. The first aim was to show possible abnormalities in timing, force and kinematic parameters of anticipatory postural adjustments in unperturbed stepping in cerebellar subjects. Second, we examined the ability of cerebellar subjects to modify anticipatory postural adjustments associated with step initiation in response to a backward translation. Finally, we asked whether cerebellar subjects (and controls) make use of predictive knowledge of perturbation amplitude in perturbed stepping. Only few abnormalities of anticipatory postural adjustments were found in cerebellar subjects compared to controls. Both in the unperturbed and perturbed step conditions, force production as well as step length and step velocity were reduced in cerebellar subjects compared to controls, suggesting compensatory slowing. Cerebellar subjects also appeared to be less able to use predictive information of perturbation amplitude to scale anticipatory postural adjustments than control subjects. Nevertheless, in unperturbed steps, temporal parameters of anticipatory postural adjustments were preserved in cerebellar subjects. When subjects voluntarily initiated a step in response to the surface translation, both control and cerebellar subjects adapted by executing the anticipatory postural adjustments for step more rapidly. Furthermore, both control and cerebellar subjects were able to use online information regarding perturbation amplitude to scale parameters of step initiation in perturbed stepping. Overall, our findings suggest that the cerebellum is neither critical for the basic motor program underlying unperturbed step initiation nor for many adaptive changes occurring during perturbed step initiation. Like its role in predictive scaling of automatic postural responses to external perturbations, the cerebellum appears to be important for predictive adaptation of anticipatory postural adjustments during step initiation.

Adolescent↗
PubMed2001

Increased variability in finger position occurs throughout overarm throws made by cerebellar and unskilled subjects.

We investigated the ability of cerebellar patients and unskilled subjects to control finger grip position and the amplitude of finger opening during a multijoint overarm throw. This situation is of interest because the appropriate finger control requires predicting the magnitude of back forces from the ball on the finger throughout the throw and generating the appropriate level and rate of change of finger flexor torque to oppose the back force. Cerebellar patients, matched controls, and unskilled subjects threw tennis balls and tennis-sized balls of different weights. In all cases angular positions of five arm segments in three dimension were recorded at 1,000 Hz with the search-coil technique as subjects threw from a seated position. When the hand was stationary, cerebellar patients showed a normal ability to grip the ball and open the fingers and drop the ball. In contrast, in overarm throws where a back force occurred on the fingers, cerebellar patients showed an abnormally large variability in amplitude of the change in finger position when gripping, in amplitude of finger opening, and in amplitude of the change in finger position 10 ms after ball release. This was not due to more trial-to-trial variation in throwing speed. When throwing balls of increasing weights, both controls and cerebellar patients had increasing finger flexions after ball release that indicated that, on average, both scaled finger force in proportion to ball weight during the throw. Unlike skilled controls, cerebellar patients showed a small (<20 degrees ) increase in the amplitude of finger opening with balls of increasing weight. However, neither the increase in variability of finger position nor the increase in finger amplitude with balls of increasing weight were unique cerebellar signs because both were observed to various degrees in unskilled throwers. It is concluded that in the absence of either normal cerebellar function or skill, the central neural activity that controls finger opening in throwing can increase finger flexor force to oppose an increase in back force from heavier balls and can open the fingers but cannot control finger force or finger opening precisely and consistently from throw to throw. These results fit with the idea that cerebellar disorders are greater in multijoint than single-joint movements because control of force is more complicated. They are also consistent with the hypothesis that the cerebellum produces skill in movement by reducing variability in the timing and force of muscle contractions.

Adolescent↗
PubMed2001

Changes in conditioned postural responses. Comparison between cerebellar patients and healthy subjects.

Postural responses elicited by external perturbation change characteristically during classical conditioning. This is assumed to be controlled by the cerebellum. In this study conditioning of postural responses in cerebellar patients was compared with that of healthy subjects. Subjects were tested when standing on a platform. Perturbations consisted of platform tilts (unconditioned stimulus, US), preceded by an auditory signal (conditioned stimulus, CS). The recording session consisted of US-alone and paired CS-US trials. In healthy subjects, unconditioned response (UR) amplitude decayed significantly with time in the recording session, especially strongly during paired trials. Amplitudes of cerebellar patients, however, decayed modestly and continuously, independently of the presence (paired trials) or otherwise of a CS. In addition, only healthy subjects established conditioned responses. Our data suggest that the prior auditory information is used to prepare postural responses. Deficits in cerebellar patients suggest a possible role of the cerebellum in controlling this plastic motor-related process.

Acoustic Stimulation↗
PubMed2000

A possible role of the human cerebellum in conditioning of the jaw-opening reflex.

The role of the human cerebellum in classical conditioning of the jaw-opening reflex was investigated using positron emission tomography (PET) in healthy subjects. The jaw-opening reflex was elicited by electrical stimulation of the right corner of the mouth (unconditioned stimulus, US). The conditioned stimulus was a tone preceding the US and coterminating with the US. Changes of regional cerebral blood flow (rCBF) were correlated with the rate of conditioning per PET scan. Conditioning effects were present in one third of all subjects. In these subjects, a significant increase of rCBF in the ipsilateral, intermediate cerebellum was shown during ongoing conditioning. Thus, the intermediate cerebellum appears to be involved in classical conditioning of the jaw-opening reflex in humans.

Adult↗
PubMed2000

Involvement of the human medial cerebellum in long-term habituation of the acoustic startle response.

Animal studies have shown an involvement of the cerebellar vermis in long-term habituation of the acoustic startle response, but not in short-term habituation. The aim of the present study was to investigate whether short-term and long-term habituation of the acoustic startle response are impaired in patients with medial cerebellar lesions. Five patients with midline cerebellar lesions due to surgery for astrocytoma and ten healthy, age- and sex-matched subjects were studied. Subjects received 40 acoustic startle stimuli each day on five successive days. Peak amplitudes of the startle response recorded at the orbicularis oculi and the sternomastoid muscles were obtained. Data were analyzed for response decrement within the training session of one day (short-term habituation) and for a decrease in the startle response across the five training days (long-term habituation). Short- and long-term habituation of the startle response recorded at the sternomastoid muscles could be achieved in controls and in cerebellar patients. However, long-term habituation of the blink component of the acoustic startle response recorded at the orbicularis oculi muscles was significantly impaired in patients with cerebellar lesions compared with control subjects, whereas short-term habituation was preserved in both groups. The present findings suggest that the medial cerebellum is involved in long-term habituation of the blink component of the startle response in humans.

Adolescent↗
PubMed2000

Classically conditioned withdrawal reflex in cerebellar patients. 1. Impaired conditioned responses.

The role of the cerebellum in the classically conditioned, human lower-limb-withdrawal reflex was studied in ten patients with pure cerebellar diseases (CBL), ten patients showing additional extracerebellar symptoms (CBL+), and in 11 sex- and age-matched normal controls (CTRL). Where conditioning was successful, the electrically evoked, unconditioned response was preceded by a tone-conditioned response (CR). CR incidence was variable, with best results in the CTRL, significantly less in CBL, and lowest in CBL+. Although CRs could be established in subjects in all groups, a continuous increase in the CR incidence in the course of the recording session was observed primarily in CTRL. In CBL and CBL+, such a characteristic reflex acquisition was rather the exception. CR onsets in CBL were within the range of those in CTRL, but CR amplitude was significantly lower in CBL. Cerebellar patients with circumscribed lesions behaved differently in our motor-learning paradigm, depending on the lesion site. Patients suffering from pathology of the posterior inferior cerebellum showed a mean CR incidence within the lower range of CTRL. In contrast, if the anterior and superior cerebellum was affected, few or even no CRs were observed. Our findings thus provide evidence that the human cerebellum is required for the acquisition and the retention of this specific conditioned limb-withdrawal reflex. In particular, anterior and superior parts of the cerebellum appear to be involved. Thus, an expansion of the current concept of clinically based, functional compartmentalization is suggested, such that anterior and superior cerebellar regions must be intact to establish plastic changes required for the acquisition of the conditioned withdrawal response.

Adult↗
PubMed2000

Classically conditioned withdrawal reflex in cerebellar patients. 2. Impaired unconditioned responses.

The study addresses the issue of the role of the cerebellum in human withdrawal-reflex conditioning by comparing data from patients with pure cerebellar diseases (CBL, n = 10) and from cerebellar patients showing additional extracerebellar symptoms (CBL+, n = 10) with those from 11 control subjects (CTRL). During recording sessions, the standard delay-conditioning paradigm with paired-trials was used with tone as the conditioned stimulus (CS). Parameters of the conditioned muscle responses are analyzed in an accompanying paper. Here, we focus on the unconditioned muscle response. A train of current pulses (unconditioned stimulus, US) evoked a lower-limb withdrawal reflex (unconditioned response, UR), which was recorded electromyographically from leg muscles. During the recording sessions with CTRL subjects, UR amplitudes decayed from initially 100% to approximately 50% at the end of the session. This type of decay was clearly less pronounced in the CBL group and minimal in the CBL+ group. Furthermore, the CBL group exhibited UR onsets that were delayed by 20 ms compared with those from CTRL subjects. Although the ranges of measurements characterizing the URs of a given cerebellar patient tested in the paired-trial paradigm overlapped with those of control subjects, the statistically significant differences observed at the group level suggest deficits in the performance of the reflex responses. The delayed URs in patients and the different type of decay of UR amplitudes in repetitively evoked withdrawal reflexes constitute evidence that the cerebellum is critically involved in the control of these UR parameters.

Adult↗
PubMed2000

Causes of left-right ball inaccuracy in overarm throws made by cerebellar patients.

Cerebellar patients throw inaccurately in the left-right direction but the cause of this multijoint ataxia is unclear. We tested whether it was due, as originally proposed, to variable left-right directions of the hand path, or, alternatively, to variable timing of ball release occurring on a right to left curved hand path. We also examined the cause of the variability in hand path direction per se. Six right-handed cerebellar patients and six control subjects were instructed to throw tennis balls at a slow, medium and fast speed from a seated position while angular positions in 3D of five arm segments were recorded at 1000 Hz with the search-coil technique. Compared to controls, cerebellar patients threw slower and less accurately, had more variable timing of ball release occurring on a right to left curved hand path and had more variable left-right directions of hand paths at a fixed point in front of the sternum. In all cerebellar patients, ball left-right inaccuracy was related both to timing of ball release and to hand path direction at the fixed point. The cause of the increased variability in hand path direction varied between patients and could not be explained by disorder in a single joint rotation. No evidence was found that it resulted from variable stabilization at the shoulder during elbow extension. Instead, the more variable left-right direction of the hand path was related to the initial pattern of joint rotations occurring early in the throw before the onset of elbow extension, and to the amplitudes of radioulnar pronation and wrist abduction occurring late in the throw. The results emphasize that in the presence of a cerebellar lesion, ball left-right inaccuracy in overarm throws cannot be explained by a single disorder. Rather ball inaccuracy was likely due to disorders in central commands to proximal joint rotations that produced the hand path and in central commands to distal joints that controlled the timing of finger opening.

Arm↗
PubMed2000

Fear conditioned potentiation of the acoustic blink reflex in patients with cerebellar lesions.

OBJECTIVE: To investigate whether the human cerebellum takes part in fear conditioned potentiation of the acoustic blink reflex. METHODS: A group of 10 cerebellar patients (eight patients with lesions involving the medial cerebellum, two patients with circumscribed lesions of the cerebellar hemispheres) was compared with a group of 16 age and sex matched healthy control subjects. The fear conditioned potentiation paradigm consisted of three phases. During the first, habituation phase subjects received 20 successive acoustic blink stimuli. In the subsequent fear conditioning phase, subjects passed through 20 paired presentations of the unconditioned fear stimulus (US; an electric shock) and the conditioned stimulus (CS; a light). Thereafter, subjects underwent the potentiation phase, which consisted of a pseudorandom order of 12 trials of the acoustic blink stimulus alone, 12 acoustic blink stimuli paired with the conditioned stimulus, and six conditioned stimuli paired with the unconditioned stimulus. The EMG of the acoustic blink reflex was recorded at the orbicularis oculi muscles. The potentiation effect was determined as the difference in normalised peak amplitude of the blink reflex evoked by pairs of CS and acoustic blink stimuli and evoked by the acoustic stimulus alone. RESULTS: In the habituation phase, short term habituation of the acoustic blink reflex was preserved in all cerebellar patients. However, in the potentiation phase, the potentiation effect of the blink reflex was significantly reduced in patients with medial cerebellar lesions compared with the controls (mean (SD) potentiation effect (%), patients: -6.4 (15.3), controls: 21.6 (35.6)), but was within normal limits in the two patients with lateral lesions. CONCLUSIONS: The present findings suggest that the human medial cerebellum is involved in associative learning of non-specific aversive reactions-that is, the fear conditioned potentiation of the acoustic blink reflex.

Adolescent↗