Florian Amtage

Task-specific changes in motor evoked potentials of lower limb muscles after different training interventions.

This study aimed to identify sites and mechanisms of long-term plasticity following lower limb muscle training. Two groups performing either a postural stability maintenance training (SMT) or a ballistic ankle strength training (BST) were compared to a non-training group. The hypothesis was that practicing of a self-initiated voluntary movement would facilitate cortico-spinal projections, while practicing fast automatic adjustments during stabilization of stance would reduce excitatory influence from the primary motor cortex. Training effects were expected to be confined to the practiced task. To test for training specificity, motor evoked potentials (MEP) induced by transcranial magnetic stimulation (TMS) were recorded at rest and during motor tasks that were similar to each training. Intracortical, cortico-spinal, as well as spinal parameters were assessed at rest and during these tasks. The results show high task and training specificity. Training effects were only observable during performance of the trained task. While MEP size was decreased in the SMT group for the trained tasks, MEP recruitment was increased in the BST group in the trained task only. The control group did not show any changes. Background electromyogram levels, M. soleus H-reflex amplitudes and intracortical parameters were unaltered. In summary, it is suggested that the changes of MEP parameters in both training groups, but not in the control group, reflect cortical motor plasticity. While cortico-spinal activation was enhanced in the BST group, SMT may be associated with improved motor control through increased inhibitory trans-cortical effects. Since spinal excitability remained unaltered, changes most likely occur on the supraspinal level.

Balance training and ballistic strength training are associated with task-specific corticospinal adaptations

The aim of this study was to investigate the role of presumably direct corticospinal pathways in long‐term training of the lower limb in humans. It was hypothesized that corticospinal projections are affected in a training‐specific manner. To assess specificity, balance training was compared to training of explosive strength of the shank muscles and to a nontraining group. Both trainings comprised 16 1‐h sessions within 4 weeks. Before and after training, the maximum rate of force development was monitored to display changes in motor performance. Neurophysiological assessment was performed during rest and two active tasks, each of which was similar to one type of training. Hence, both training groups were tested in a trained and a nontrained task. H‐reflexes in soleus (SOL) muscle were tested in order to detect changes at the spinal level. Corticospinal adaptations were assessed by colliding subthreshold transcranial magnetic stimulation to condition the SOL H‐reflex. The short‐latency facilitation of the conditioned H‐reflex was diminished in the trained task and enhanced in the nontrained task. This was observable in the active state only. On a functional level, training increased the rate of force development suggesting that corticospinal projections play a role in adaptation of leg motor control. In conclusion, long‐term training of shank muscles affected fast corticospinal projections. The significant interaction of task and training indicates context specificity of training effects. The findings suggest reduced motor cortical influence during the trained task but involvement of direct corticospinal control for new leg motor tasks in humans.

[18F]FDG-PET is superior to [123I]IBZM-SPECT for the differential diagnosis of parkinsonism

Objective: Imaging of regional cerebral glucose metabolism with PET and striatal dopamine D2/D3 receptors (D2R) with SPECT improves the differential diagnosis of parkinsonism. We prospectively investigated 1) the diagnostic merits of these approaches in differentiating between Lewy body diseases (LBD; majority Parkinson disease [PD]) and atypical parkinsonian syndromes (APS); 2) the diagnostic value of [18F]fluorodeoxyglucose (FDG)-PET to differentiate among APS subgroups. Methods: Ninety-five of 107 consecutive patients with clinically suspected APS referred for imaging were recruited. [18F]FDG-PET scans were analyzed by visual assessment (including individual voxel-based statistical maps). Based on a priori defined disease-specific patterns, patients with putative APS were differentiated from LBD (first level) and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD) (second level). [123I] iodobenzamide (IBZM)-SPECT datasets were subjected to an observer-independent regions-of-interest analysis to assess striatal D2R availability. Movement disorder specialists made final clinical diagnoses after a median follow-up time of 12 months. Results: Seventy-eight patients with clinically verified APS (n = 44) or LBD (n = 34) were included in the statistical analysis. The area under the receiver operating characteristic curve for discrimination between APS and LBD was significantly larger for [18F]FDG-PET (0.94) than for [123I]IBZM-SPECT (0.74; p = 0.0006). Sensitivity/specificity of [18F]FDG-PET for diagnosing APS was 86%/91%, respectively. Sensitivity/specificity of [18F]FDG-PET in identifying APS subgroups was 77%/97% for MSA, 74%/95% for PSP, and 75%/92% for CBD. Conclusions: The diagnostic accuracy of [18F]FDG-PET for discriminating LBD from APS is considerably higher than for [123I]IBZM-SPECT. [18F]FDG-PET reliably differentiates APS subgroups.

Impact of a Weekly Dance Class on the Functional Mobility and on the Quality of Life of Individuals with Parkinson’s Disease

Individuals with Parkinson’s disease (PD) mainly suffer from motor impairments which increase the risk of falls and lead to a decline of quality of life. Several studies investigated the long-term effect of dance for people with PD. The aims of the present study were to investigate (i) the short-term effects of dance (i.e., the effect immediately after the dance class) on motor control in individuals with PD and (ii) the long-term effects of 8 months of participation in the weekly dance class on the quality of life of the PD patients and their caregivers. The dance lessons took place in a ballet studio and were led by a professional dancer. Eleven people with moderate to severe PD (58–85 years old) were subjected to a motor and quality of life assessments. With respect to the motor assessments the unified Parkinson disease rating scale III (UPDRS III), the timed up and go test (TUG), and the Semitandem test (SeTa) before and after the dance class were used. With respect to the quality of life and well-being we applied quality of life scale (QOLS) as well as the Westheimer questionnaire. Additionally, we asked the caregivers to fill out the Questionnaire for caregivers. We found a significant beneficial short-term effect for the total score of the UPDRS motor score. The strongest improvements were in rigidity scores followed by significant improvements in hand movements, finger taps, and facial expression. No significant changes were found for TUG and for SeTa. The results of the questionnaires showed positive effects of the dance class on social life, health, body-feeling and mobility, and on everyday life competences of the PD patients. Beneficial effect was also found for the caregivers. The findings demonstrate that dance has beneficial effect on the functional mobility of individuals with PD. Further, dance improves the quality of life of the patients and their caregivers. Dance may lead to better therapeutic strategies as it is engaging and enjoyable.

Tremor-correlated neuronal activity in the subthalamic nucleus of Parkinsonian patients

Tremor in Parkinsons disease (PD) is generated by an oscillatory neuronal network consisting of cortex, basal ganglia and thalamus. The subthalamic nucleus (STN) which is part of the basal ganglia is of particular interest, since deep brain stimulation of the STN is an effective treatment for PD including Parkinsonian tremor. It is controversial if and how the STN contributes to tremor generation. In this study, we analyze neuronal STN activity in seven patients with Parkinsonian rest tremor who underwent stereotactic surgery for deep brain stimulation. Surface EMG was recorded from the wrist flexors and extensors. Simultaneously, neuronal spike activity was registered in different depths of the STN using an array of five microelectrodes. After spike-sorting, spectral coherence was analyzed between spike activity of STN neurons and tremor activity. Significant coherence at the tremor frequency was detected between EMG and neuronal STN activity in 76 out of 145 neurons (52.4%). In contrast, coherence in the beta band occurred only in 10 out of 145 neurons (6.9%). Tremor-coherent STN activity was widely distributed over the STN being more frequent in its dorsal parts (70.8-88.9%) than in its ventral parts (25.0-48.0%). Our results suggest that synchronous neuronal STN activity at the tremor frequency contributes to the pathogenesis of Parkinsonian tremor. The wide-spread spatial distribution of tremor-coherent spike activity argues for the recruitment of an extended network of subthalamic neurons for tremor generation.

A disease-specific metabolic brain network associated with corticobasal degeneration

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (∼ 24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes.

Characterization of nicotinic receptors inducing noradrenaline release and absence of nicotinic autoreceptors in human neocortex

UNLABELLED Presynaptic facilitatory nicotinic receptors (nAChRs) on noradrenergic axon terminals were studied in slices of human or rat neocortex and of rat hippocampus preincubated with [3H]noradrenaline ([3H]NA). During superfusion of the slices, stimulation by nicotinic agonists for 2 min only slightly increased [3H]NA outflow in the rat neocortex, but caused a tetrodotoxin-sensitive. Ca(2+)-dependent release of [3H]NA in rat hippocampus and human neocortex. In both tissues a similar rank order of potency of nicotinic agonists was found: epibatidine >> DMPP > nicotine approximately cytisine > or = acetylcholine; choline was ineffective. In human neocortex, the effects of nicotine (100 microM) were reduced by mecamylamine, methyllycaconitine, di-hydro-beta-erythroidine (10 microM, each) and the alpha3beta2/alpha6betax-selective alpha-conotoxin MII (100/200 nM). The alpha3beta4 selective alpha-conotoxin AuIB (1 microM), and the alpha7 selective alpha-conotoxin ImI (200 nM) as well as alpha-bungarotoxin (125 nM) were ineffective. Glutamate receptor antagonists (300 microM AP-5, 100 microM DNQX) acted inhibitory, suggesting the participation of nAChRs on glutamatergic neurons. On the other hand, nAChR agonists were unable to evoke exocytotic release of [3H]acetylcholine from human and rat neocortical slices preincubated with [3H]choline. IN CONCLUSION (1) alpha3beta2 and/or alpha6 containing nAChRs are at least partially responsible for presynaptic cholinergic facilitation of noradrenergic transmission in human neocortex; (2) nicotinic autoreceptors were not detectable in rat and human neocortex.

Differentiation of neurodegenerative parkinsonian syndromes by volumetric magnetic resonance imaging analysis and support vector machine classification.

Clinical differentiation of parkinsonian syndromes is still challenging.

Neurotransmitter release and its presynaptic modulation in the rat hippocampus after selective damage to cholinergic or/and serotonergic afferents

UNLABELLED Male Long-Evans rats sustained injections of 5,7-dihydroxytryptamine (5,7-DHT) into the fimbria-fornix and the cingular bundle or/and intraseptal injections of 192 IgG-saporin to induce serotonergic or/and cholinergic hippocampal denervations; Sham-operated rats served as controls. Four to ten weeks after lesioning, we measured (i). the electrically evoked release of acetylcholine ([3H]ACh), noradrenaline ([3H]NA) and serotonin ([3H]5-HT) in hippocampal slices in the presence of drugs acting on auto- or heteroreceptors, (ii). the nicotine-evoked release of NA and (iii). the choline acetyltransferase (ChAT) activity and the concentration of monoamines in homogenates. Saporin lesions reduced the accumulation of [3H]choline, the release of [3H]ACh and the ChAT activity, but increased the concentration of NA and facilitated the release of [3H]NA evoked by nicotine. 5,7-DHT lesions reduced the accumulation and the release of [3H]5-HT, the concentration of 5-HT, and also facilitated the release of [3H]NA evoked by nicotine. Accumulation and electrically evoked release of [3H]NA were not altered by either lesion. The combination of both toxins resulted in an addition of their particular effects. The 5-HT(1B) receptor agonist, CP 93129, and the muscarinic agonist, oxotremorine, reduced the release of [3H]ACh in control and 5,7-DHT-lesioned rats; in rats injected with saporin, their effects could not be measured reliably. CP 93129 and the alpha(2)-adrenoceptor agonist, UK 14304, reduced the release of [3H]5-HT in all groups by about 65%. IN CONCLUSION (i). selective neurotoxins can be combined to enable controlled and selective damage of hippocampal transmitter systems; (ii). 5-HT exerts an inhibitory influence on the nicotine-evoked release of NA, but partial serotonergic lesions do not influence the release of ACh at a presynaptic level and (iii). presynaptic modulatory mechanisms involving auto- and heteroreceptors may be conserved on fibres spared by the lesions.

High functional connectivity of tremor related subthalamic neurons in Parkinson’s disease

OBJECTIVE Tremor is a core symptom of Parkinsons disease (PD). The subthalamic nucleus (STN) seems to be crucial for tremor pathophysiology considering that deep brain stimulation (DBS) of the STN leads to an effective reduction of Parkinsonian tremor. Here, we investigate the functional connectivity between STN neurons in patients with Parkinsonian tremor. METHODS STN activity was analyzed in 7 patients with Parkinsonian rest tremor who underwent stereotactic surgery for DBS. Spike activity was registered in different depths of the STN using an array of five microelectrodes. Interneuronal coherence within the STN was analyzed. RESULTS Significant interneuronal coherence at the tremor frequency was detected in 78 out of 145 neurons. In contrast, interneuronal coherence in the beta band occurred only in 26 out of 145 neurons. Functional connectivity at the tremor frequency can be characterized by a slowly decaying exponential curve which describes coherence between STN neurons as a function of interneuronal distances between 0 and 4mm. CONCLUSIONS Spatially distributed synchronization at the tremor frequency seems to be a key feature of STN pathophysiology in patients with Parkinsonian tremor. SIGNIFICANCE The findings suggest a subthalamic tremor network which is widely extended and strongly coupled.