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Biomedical subjects

Reinhard Dengler

Publications and source records attributed to Reinhard Dengler.

45 records · Page 3Linked to original sources
PubMed2002

Decrease of middle cerebral artery blood flow velocity after low-frequency repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been tried therapeutically in a variety of neuropsychiatric disorders. Both, inhibition and activation of cortical areas may be achieved using different stimulation parameters. Using low-frequency rTMS (0.9 Hz), inhibition of cortical areas can be observed. METHODS: In the present study, 38 right-handed, healthy, normotensive subjects (aged 21-50 years, mean 30.2 years, SD=4.9; 17 women) were enrolled. Twenty-five participants received active rTMS (5 min of 0.9 Hz rTMS, stimulus intensity 90% of motor threshold) of the right dorsolateral prefrontal cortex. Sham stimulation (n=13 subjects) occurred in the same manner as active rTMS, except that the angle of the coil was at 45 degrees off the skull. Simultaneously, ipsilateral and contralateral maximal middle cerebral artery (MCA) flow velocity (and pulsatility index, PI) was monitored using transcranial Doppler sonography. RESULTS: In the group with active rTMS, maximal MCA flow velocity decreased from a baseline (before rTMS) of 101.6 cm/s (SD=26.0) to a mean of 92.6 cm/s (SD=23.7) immediately after rTMS, T=5.06, P<0.001. This equals a mean decrease of 9.0 cm/s (SD=8.3) or approximately 8.9% of baseline flow. Five and 10 min after rTMS, there was a return to baseline. PI significantly decreased 10 min after rTMS (mean difference -0.05, SD=0.05, T=2.29, P<0.05). In the contralateral MCA, maximal flow velocity tended to increase 10 min after rTMS (mean difference +7.4 cm/s, SD=17.5; T=-2.03, P=0.054). With sham rTMS, no significant changes occurred. CONCLUSIONS: The results from our study support the hypothesis that low-frequency rTMS may influence cerebral blood flow (CBF) over short periods of time, inducing a temporary decrease of maximal CBF in the ipsilateral MCA followed by an increase in the contralateral MCA.

Adult↗
PubMed2002

Block of voltage-operated sodium channels by 2,6-dimethylphenol, a structural analogue of lidocaine's aromatic tail.

1. The structural features that determine the state-dependent interaction of local anaesthetics with voltage-operated sodium channels are still a matter of debate. We have studied the blockade of sodium channels by 2,6-dimethylphenol, a phenol derivative which resembles the aromatic tail of lidocaine, etidocaine, and bupivacaine. 2. The effects of 2,6-dimethylphenol were studied on heterologously (HEK 293) expressed rat neuronal (rat brain IIA) and human skeletal muscle (hSkM1) sodium channels using whole-cell voltage-clamp experiments. 3. 2,6-Dimethylphenol was effective in blocking whole-cell sodium inward currents. Its potency was comparable to the potency of lidocaine previously obtained with similar protocols by others. The IC(50) at -70 mV holding potential was 150 and 187 microM for the skeletal muscle and the neuronal isoform, respectively. In both isoforms, the blocking potency increased with the fraction of inactivated channels at depolarized holding potentials. However, the block achieved at -70 mV with respect to -150 mV holding potential was significantly higher only in the skeletal muscle isoform. The estimated dissociation constant K(d) from the inactivated state was 25 microM and 28 microM in the skeletal muscle and the neuronal isoform, respectively. The kinetics of drug equilibration between resting and inactivated channel states were about 10 fold faster compared with lidocaine. 4. Our results show that the blockade induced by 2,6-dimethylphenol retains voltage-dependency, a typical feature of lidocaine-like local anaesthetics. This is consistent with the hypothesis that the 'aromatic tail' determines the state-dependent interaction of local anaesthetics with the sodium channel.

Cell Line↗
PubMed2002

Control of kinetic properties of GluR2 flop AMPA-type channels: impact of R/G nuclear editing.

The GluR2 flop subunit of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors greatly determines calcium permeability and kinetic properties of heteromeric AMPA subunit assemblies. Post-transcriptional editing of this subunit at the Q/R/N site controls calcium permeability whereas editing at the R/G site is involved in the regulation of biophysical properties. We used patch-clamp techniques with ultrafast solution exchange to examine the kinetics of recombinant human homomeric GluR2 flop channels transiently expressed in HEK293 cells [edited at the R/G site and Q/R/N site (GR), and unedited (RN) and edited (GN) at the R/G site both with asparagine (N) at the Q/R/N site]. The time constant of desensitization after application of 10 mm glutamate was 1.38 +/- 0.05 ms (n = 10), 5.53 +/- 0.57 ms (n = 7) and 1.33 +/- 0.06 ms (n = 12) for the GluR2 flop GR, RN and GN channels, respectively. The time constant of resensitization was 75 ms for the GluR2 flop RN and 30 ms for the GN channels. The dose-dependence of the peak current amplitude, kinetics of activation and deactivation, and peak open probability did not differ between RN and GN channels. The study shows that desensitization and resensitization kinetics of homomeric GluR2 flop channels are controlled by a single amino acid exchange (glycine by arginine) at the R/G site. Quantitative analysis by computer simulation using a circular kinetic scheme allows the prediction of the main experimental results.

Algorithms↗
PubMed2002

The effects of proprioceptive stimulation on cognitive processes in patients after traumatic brain injury.

OBJECTIVE: To investigate the hypothesis that proprioceptive stimulation may be effective in the treatment of brain injury, using neurophysiologic and neuropsychologic measures. DESIGN: Cohort analytic study. SETTING: Patients recovering from traumatic brain injury (TBI) in a neurologic rehabilitation hospital were examined. PARTICIPANTS: Eleven patients with TBI (Glasgow Coma Scale score > 3) and 11 healthy control subjects matched for age and education. INTERVENTIONS: Subjects were examined with the event-related potential (ERP) technique during a computerized choice-reaction-time task, in which they had to discriminate between even and odd digits. There were experimental runs with and without vibratory stimuli applied to the left forearm serving as proprioceptive stimulation. In addition, ERPs were recorded to vibratory stimuli without any additional task. MAIN OUTCOME MEASURES: Outcome measures included latencies and amplitudes of the P300 ERP component and of the late negative component. RESULTS: In the passive vibration condition, both groups showed the same ERP distribution. In the choice-reaction-time task, latencies and amplitudes of the P300 differed between the 2 groups. The patient group showed longer P300 latencies, which were shortened by vibratory stimuli. In contrast, the control subjects were not affected by vibratory stimuli. CONCLUSION: Our findings support the hypothesis that pathologic cognitive processes after TBI can be improved by proprioceptive stimulation. Muscle vibration has positive effects on pathologically slowed cognitive processes but not in healthy subjects.

Adult↗
PubMed2002

Disturbance of "extrinsic alertness" in Huntington's disease.

Neuropsychological deficits are a main feature of Huntington's disease (HD) with previous data suggesting involvement of attentional functions. Attention can be divided into several different dimensions: intensity, selectivity and supervisory attentional control. These different aspects of attention were investigated in a group of 13 patients with HD and 13 healthy matched control subjects. HD patients were impaired mostly for the intensity dimension: contrary to controls, and like other neurological patient groups, they were not able to speed up their reaction times when an auditory warning stimulus preceded a visual target which suggests a deficit in 'extrinsic alertness.' In addition less severe impairments were found in the dimensions selectivity and supervisory attentional control.

Adult↗
PubMed2002

Impaired sensorimotor integration in cervical dystonia: a study using transcranial magnetic stimulation and muscle vibration.

The authors studied the effects of sensorimotor integration (corticocortical inhibition and facilitation during muscle vibration [MV]) in dystonic patients. Eleven patients with cervical dystonia and 11 age-matched healthy control subjects were enrolled in the study. They were examined using transcranial magnetic stimulation (TMS) and tonic proprioceptive input (MV). Paired-pulse transcranial magnetic stimulation was done at interstimulus intervals of 3 msec (intracortical inhibition) and 13 msec, the intensity of the conditioning stimulus was 70% of the motor threshold, and the test stimulus was 120%. Motor evoked potentials were recorded from the vibrated extensor carpi radialis muscle and its antagonist, the flexor carpi radialis. Duration of MV trains (80 Hz; amplitude, 0.5 mm) was 4 seconds. The authors found differences between patients and healthy control subjects during MV only. Intracortical inhibition was pronounced significantly only in control subjects, whereas intracortical facilitation was significant in patients only (P < 0.05). Furthermore, the significant reduction of motor evoked potentials at 13-msec interstimulus intervals, which can be found in healthy subjects frequently, was observed in one dystonia patient only. The results of the current study suggest that sensorimotor integration is impaired in cervical dystonia, probably by an altered control of proprioceptive (vibratory) input.

Adult↗
PubMed2002

Repetitive transcranial magnetic stimulation for the treatment of chronic pain - a pilot study.

Invasive electrical stimulation of the motor cortex has been reported to be of therapeutic value in pain control. We were interested whether noninvasive repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex might also act beneficially. Twelve patients with therapy-resistant chronic pain syndromes (mean age 51.3 +/- 12.6, 6 males) were included in a pilot study. They were treated with rTMS of the corresponding motor cortex area for 20 min (20 Hz, 20 x 2 s trains, intensity 80% of motor threshold) and sham stimulation (sequence-controlled cross-over design). Some of the patients (6/6) had an analgesic effect, but for the whole group, the difference between active and sham stimulation did not reach a level of significance (active rTMS: mean VAS reduction -4.0 +/- 15.6%; sham rTMS: -2.3 +/- 8.8%). Further studies using different rTMS stimulation parameters (duration and frequency of rTMS) or stimulation sites (e.g. anterior cingulate gyrus) are strongly encouraged.

Adult↗
PubMed1998

Cortical auditory disorders: a case of non-verbal disturbances assessed with event-related brain potentials.

In the auditory modality, there has been a considerable debate about some aspects of cortical disorders, especially about auditory forms of agnosia. Agnosia refers to an impaired comprehension of sensory information in the absence of deficits in primary sensory processes. In the non-verbal domain, sound agnosia and amusia have been reported but are frequently accompanied by language deficits whereas pure deficits are rare. Absolute pitch and musicians' musical abilities have been associated with left hemispheric functions. We report the case of a right handed sound engineer with the absolute pitch who developed sound agnosia and amusia in the absence of verbal deficits after a right perisylvian stroke. His disabilities were assessed with the Seashore Test of Musical Functions, the tests of Wertheim and Botez (Wertheim and Botez, Brain 84, 1961, 19-30) and by event-related potentials (ERP) recorded in a modified 'oddball paradigm'. Auditory ERP revealed a dissociation between the amplitudes of the P3a and P3b subcomponents with the P3b being reduced in amplitude while the P3a was undisturbed. This is interpreted as reflecting disturbances in target detection processes as indexed by the P3b. The findings that contradict some aspects of current knowledge about left/right hemispheric specialization in musical processing are discussed and related to the literature concerning cortical auditory disorders.

Journal Article↗