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D Timmann

Publications and source records attributed to D Timmann.

At least 19 recordsLinked to original sources
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↗
PubMed2000

Predictive control of muscle responses to arm perturbations in cerebellar patients.

OBJECTIVES: To examine changes in predictive control of early antagonist responses to limb perturbations in patients with defined lesions of the cerebellum. METHODS: Eight cerebellar patients and eight sex and age matched control subjects participated. Subjects held a handle that was rotated around the elbow joint. They were instructed to hold the forearm at 90 degrees flexion against a mechanical perturbation. Extensor torque (5 Nm) was applied for 140 ms (pulse), or for 1400 ms (step) through an external motor. Motor responses were tested under two different conditions of anticipatory information. In the expected condition, subjects anticipated and received a pulse. Under the unexpected condition, subjects expected steps, but received unexpected pulses. Biceps and triceps EMG as well as angular kinematics were compared between expected and unexpected pulse perturbations to quantify possible effects of prediction. RESULTS: In all healthy subjects, the degree of overshoot in the return flexion movement was significantly less in expected pulse perturbations compared with unexpected trials. The degree of amplitude reduction was significantly smaller in the patient group than in the control group (22.8% v 40.0%). During the expected trials, latency of peak triceps activity was on average 20% shorter in the control group, but 4% larger in the cerebellar patients. CONCLUSIONS: In the expected condition, controls achieved a significant reduction in angular amplitude by generating triceps activity earlier, whereas the ability to use prediction for adjusting early antagonist responses after limb perturbation was impaired in cerebellar patients.

Adolescent↗
PubMed1999

A kinematic study of progressive apraxia with and without dementia.

BACKGROUND: Prehension is an ideationally simple, cued movement requiring proximal (transport) and distal (manipulation) limb control. Patients with this syndrome of progressive apraxia are unable to perform many activities of daily living that require prehension. There is little known about how this syndrome kinematically disrupts such movements or whether concurrent dementia might play a critical role. OBJECTIVES: Using prehension as a paradigm for an ideationally simple, cued functional movement, we sought to (1) characterize the kinematic features of progressive apraxia in general, and (2) contrast the kinematic differences between apraxic patients with and without dementia. METHODS: Eight patients with the syndrome of progressive apraxia (including five without dementia, one of whom had autopsy-confirmed corticobasal ganglionic degeneration, and three with dementia, one of whom had autopsy-confirmed Alzheimer's disease) were compared with eight age-matched normal control subjects on a prehension task using an Optotrak camera system. RESULTS: Compared with control subjects, apraxic subjects had slowed reaction time, slowed transport and manipulation kinematics, greater lateral deviation from the linear prehension trajectory, greater intermanual asymmetry, motor programming disturbances, and mild transport-manipulation uncoupling. There were minor differences between the apraxia subgroups such as greater intermanual differences and impaired grip aperture velocity in the nondemented group, and overall slower movement in the demented group. CONCLUSIONS: There are major kinematic differences between apraxic and control subjects on a prehension task. The differences between clinical-pathologic subgroups are more subtle, and the movement disorder itself rather than concurrent dementia is the greatest determinant of motor disability.

Aged↗
PubMed1999

Non-motor associative learning in patients with isolated degenerative cerebellar disease.

In recent decades it has become clear that the cerebellum is involved in associative motor learning, but its exact role in motor learning as such is still controversial. Recently, a contribution of the cerebellum to different cognitive abilities has also been considered, but it remains unclear whether the cerebellum contributes to cognitive associative learning. We compared nine patients with an isolated cerebellar degenerative disease in a cognitive associative learning task with 10 controls. Patients and controls were matched for age, sex, handedness, level of education, intelligence and capabilities of visual memory. The subjects were asked to learn the association between six pairs of colours and numerals by trial and error. Additionally, a simple reaction time and a visual scanning test were conducted in order to control for the influence of motor performance deficits in cerebellar patients. In comparison with the controls, it took the patients significantly longer to learn the correct associations between colours and numerals, and they were impaired in recognizing them later on. Two patients showed no associative learning effect at all. Neither the simple reaction time nor the visual scanning time correlated substantially with the results of associative learning. Therefore, motor-associated disabilities are unlikely to be the reason for the learning deficit in cerebellar patients. Our results suggest that the cerebellum might contribute to motor-independent processes that are generally involved in associative learning.

Aged↗
PubMed1999

Failure of cerebellar patients to time finger opening precisely causes ball high-low inaccuracy in overarm throws.

We investigated the idea that the cerebellum is required for precise timing of fast skilled arm movements by studying one situation where timing precision is required, namely finger opening in overarm throwing. Specifically, we tested the hypothesis that in overarm throws made by cerebellar patients, ball high-low inaccuracy is due to disordered timing of finger opening. Six cerebellar patients and six matched control subjects were instructed to throw tennis balls at three different speeds from a seated position while angular positions in three dimensions of five arm segments were recorded at 1,000 Hz with the search-coil technique. Cerebellar patients threw more slowly than controls, were markedly less accurate, had more variable hand trajectories, and showed increased variability in the timing, amplitude, and velocity of finger opening. Ball high-low inaccuracy was not related to variability in the height or direction of the hand trajectory or to variability in finger amplitude or velocity. Instead, the cause was variable timing of finger opening and thereby ball release occurring on a flattened arc hand trajectory. The ranges of finger opening times and ball release times (timing windows) for 95% of the throws were on average four to five times longer for cerebellar patients; e.g., across subjects mean ball release timing windows for throws made under the medium-speed instruction were 11 ms for controls and 55 ms for cerebellar patients. This increased timing variability could not be explained by disorder in control of force at the fingers. Because finger opening in throwing is likely controlled by a central command, the results implicate the cerebellum in timing the central command that initiates finger opening in this fast skilled multijoint arm movement.

Adolescent↗
PubMed1998

Perturbed step initiation in cerebellar subjects. 1. Modifications of postural responses.

Recent experiments in healthy subjects have demonstrated that automatic postural responses can be suppressed when subjects are instructed to step instead of maintain stance in response to the surface translation. The aim of the present study was to investigate the role of the cerebellum in coordinating this interaction between the central command to step and peripherally triggered automatic postural responses. Eight subjects with cerebellar degeneration and eight control subjects were instructed to either maintain stance or step forward in response to a backward translation. In order to determine whether prediction of perturbation amplitude assisted suppression of postural responses, three platform translations were presented in both a serial (predictable) and a random (unpredictable) order. Cerebellar subjects were able to suppress their initial postural responses to the same amount as control subjects when instructed to step forward in response to backward translations, despite their hypermetria and inability to scale responses to predictable perturbation amplitudes. Control, but not cerebellar, subjects scaled the size of their postural responses to predictable perturbation amplitudes. The perturbation amplitude, however, had no effect on the size of early automatic responses when they were suppressed by instruction to step. The size of the suppressed postural response was independent of predictability of perturbation amplitudes in both control and cerebellar subjects. The dynamic interaction between automatic postural responses to an external perturbation and anticipatory postural adjustments for step initiation seems independent of prediction of perturbation amplitude and the integrity of the cerebellum. Although cerebellar subjects show larger-than-normal magnitude and variability of postural responses and an inability to scale the size of responses to predictable perturbation amplitudes, the cerebellum does not seem to be critical for suppression of the early postural response with a centrally intended movement.

Adaptation, Physiological↗
PubMed1998

Postural responses to changing task conditions in patients with cerebellar lesions.

OBJECTIVE: To investigate the role of the cerebellum in postural adaptation for changes to the stimulus type of support surface displacements (backward translations v "toes up" rotations). METHODS: A group of 13 patients with chronic, isolated lesions of the cerebellum and 15 control subjects were tested. Automatic postural responses of the medial gastrocnemius and anterior tibial muscles were recorded. The first paradigm consisted of 10 rotational perturbations followed by 10 backward translations of the platform, and 10 backward translations followed by 10 rotations. The second paradigm consisted of 18 rotations and two randomly interposed translational perturbations, and 18 translations with two rotations randomly interposed. RESULTS: When the type of perturbation changed from an expected translation to an unexpected rotation and vice versa both control subjects and cerebellar patients showed an immediate and significant change in the response amplitude of the medial gastrocnemius and at the same time an immediate and significant change in the response amplitude of the anterior tibial muscles. Neither controls nor cerebellar patients showed effects of prediction in surface displacements of unexpected types of perturbation. Both controls and cerebellar patients showed no gradual increase in the gastrocnemius response in subsequent trials of surface translations following a block of 10 surface rotations and no gradual increase in the response amplitude of the anterior tibial muscle in subsequent trials of surface rotations following a block of 10 surface translations. CONCLUSIONS: Despite postural hypermetria, the integrity of the cerebellum does not seem critical for adaptation of postural synergies to changing stimulus types of surface displacements. The present results support previous findings suggesting that the main role of the cerebellum in automatic postural responses may be gain control.

Adult↗
PubMed1998

Involvement of the human cerebellum during habituation of the acoustic startle response: a PET study.

The present study investigated the involvement of the human cerebellum in the habituation of the acoustic startle response using PET. The startle response was elicited in seven young, healthy subjects by a tone presented via headphones. Startle responses were recorded from the right sternocleidomastoid muscle. Regional cerebral blood flow (rCBF) was assessed in nine scans and one startle stimulus was applied during each scan. The reduction of size of the sternocleidomastoid muscle response was correlated with changes in rCBF during the ongoing process of startle response habituation. A significant decrease of rCBF was found in the medial cerebellum. These data are consistent with an involvement of the medial parts of the human cerebellum in non-associative learning as proposed by previous animal studies.

Acoustic Stimulation↗
PubMed1997

A reliable method for sustaining a pre-defined pre-innervation level.

Numerous experimental approaches are based on evaluating electromyographically recorded muscle activity. Some experiments require a certain level of pre-innervation in a muscle or muscle group whereas others must avoid this. Measured parameters, such as the time to onset of the muscle response to an electrical stimulus, etc., depend critically on the level of pre-innervation. The pre-innervation level is most commonly estimated from parameters such as the force generated by this muscle or the upright posture of a human subject. These methods, however, are indirect and may yield erroneous results. This paper describes an inexpensive method developed for a wide range of applications in muscle-tonus-based experiments, in which the tonus is precisely controlled. A simple electronic circuit is presented by which the level of muscle pre-innervation is directly recorded, monitored and - depending on the experimental approach - also fed back to the subject. Physiological experiments on the flexion reflex in healthy human subjects document the reliability of our electronic device.

Electromyography↗
PubMed1997

Side effects from increased doses of carbamazepine on neuropsychological and posturographic parameters of humans.

Patients taking anticonvulsant drugs display a broad spectrum of side-effects. Particularly, in the beginning of treatment and with increasing doses of carbamazepine, side effects such as dizziness, ataxia, drowsiness and reduction of alertness occur, which improve some days after the dose has reached a stable level. Our aim was to find objective parameters for grading these side effects and to differentiate between neurophysiological and neuropsychological side effects of carbamazepine in a clinical situation. Twenty-two patients with trigeminal neuralgia were included for a follow-up study with increasing carbamazepine doses (0 mg to 600 mg). The effect of carbamazepine on postural stability was quantified by posturography. Different neuropsychological tests to study cognitive effects of carbamazepine were performed. The composite equilibrium score showed a significant reduction of postural stability with increasing doses of carbamazepine. In sensory analysis the somatosensory ratio was significantly influenced by increased doses of carbamazepine during the study. Mean reaction time of tonic alertness and physical alertness varied significantly with different doses of carbamazepine. There was a significant influence in patients attention during trail making tests and divided attention tests with increase in carbamazepine. In conclusion our observations show that the rate of change of carbamazepine doses is an important determinant of cognitive and motor functions in the phase of increasing doses.

Adult↗
PubMed1997

Prediction and set-dependent scaling of early postural responses in cerebellar patients.

We reported previously that patients with cerebellar deficits were unable to scale the magnitude of their early automatic postural responses to the predicted amplitudes of surface translations based on central set from prior experience. The present study investigated whether this deficit in set-dependent amplitude scaling was based predominantly on the cerebellar patient's disability (i) to predict perturbation amplitudes on the basis of prior experience, (ii) to scale the gain or magnitude of upcoming postural responses or (iii) to habituate postural responses. The increase in size of the early postural response when a larger than actual platform amplitude was expected and decrease when a smaller one was expected was defined as a measure of set-dependent amplitude prediction. The suppression of the postural response when the same platform velocity was repeated was used as a measure of habituation. The correlation between the size of early postural responses and platform amplitudes when presented serially, but not randomly, tested the ability to scale the gain of postural responses based on prior experience. Results show that although cerebellar patients could predict perturbation amplitudes based on prior experience, they could not use this prediction to modify precisely the gain of responses. The ability to habituate the magnitude of postural responses was not affected by cerebellar lesions. Thus, the cerebellum might not be critical for predicting upcoming events or for habituating to repeated postural stimuli, although it is important for accurate tuning of response gain based on prediction.

Adult↗
PubMed1996

Cerebellar activation during classical conditioning of the human flexion reflex: a PET study.

The present study investigated the involvement of the cerebellum in classical conditioning of the cutaneomuscular flexion reflex in four normal volunteers using positron emission tomography (PET). The flexion reflex was elicited by electrical pulses applied to the medial plantar nerve (unconditioned stimulus, US). A tone was presented as the conditioning stimulus, which co-terminated with the US. The incidence of conditioned responses was correlated with changes in rCBI during the acquisition process of flexion reflex conditioning. Blood flow was significantly increased in an area extending from the ipsilateral cerebellum and hippocampus to bilateral frontal regions (p = 0.009). These data provide support for an involvement of the cerebellum as well as hippocampus among other neural systems in classical flexion reflex conditioning.

Adult↗