P162 Alien hand syndrome: Neural correlates of movements without conscious will

Abstract / Basal Ganglia 1 (2011) 13–45

kinetic rigid symptoms. In these diseases characteristic MRI T1hyperintensities of the putamen were described. In the here presented study we examined the frequency of a hypokinetic rigid syndrome in patients with cirrhosis of the liver. We tested the serum copper and manganese concentrations in these patients, performed a cerebral MRI a UPDRS motorscale and a levodopa-test. Results: Of the first 10 examined patients suffering from cirrhosis of the liver 9 showed a differentially pronounced hypokinetic rigid syndrome (UPDRS motorscale between 3 and 53 points). The symptom rigidity was present in all of these patients. The two patients with the highest values in the UPDRS motorscale (53 and 39 points) also had by far the highest manganese serum concentrations: 26.7 and 27.3 lg/l (normal value <11 lg/l). Patients with lower values in the UPDRS motorscale had mildly elevated or normal manganese levels. Likewise had control patients suffering from idiopathic Parkinson’s disease (PD) or multisystem atrophy (MSA) normal manganese values. In contrast to these findings copper values showed no correlation to the clinical syndrome. In no case a patient showed a clinical improvement of its hypokinetic rigid syndrome in the levodopa-test. The patient with the highest manganese level (27.3 lg/l) and an UPDRS motorscale of 39 points also showed the highest measured intensity values in the putamen (475.70 left/472.63 right, arbitrary units (AU)). Also patients with a milder hypokinetic rigid syndrome showed a hyperintense signal in the putamen of about 200 AU. On the contrary control patients suffering from PD or MSA showed intensity values of about 125 AU. Conclusions: According to our control sample an, although partially mild, hypokinetic rigid syndrome seems frequent in patients suffering from cirrhosis of the liver. This syndrome was not levodopa responsive. The syndrome correlated with elevated manganese serum levels and in cerebral MRI with T1 hyperintensities of the putamen. doi:10.1016/j.baga.2011.01.079

P160 Effect of botulinum toxin on force regulation in patients with writer’s cramp L. Pedack, A. Knutzen, G. Deuschl, J. Volkmann, K.E. Zeuner (Kiel) Background: Characteristic for writer’s cramp are involuntary cocontractions of antagonist muscles during writing. Sensorimotor processing of muscle spindle afferent discharges are abnormal, and improper force regulation has been attributed to disturbed sensorimotor integration. With Botulinumtoxin (BTX) injections affected muscles are weakened to improve dystonic symptoms, but BTX might have additional effects on spindle afferents. We measured force regulation before and after BTX treatment and expected improvement of disturbed force regulation after the injections. Methods: Fourteen patients (age 54 ± 10 years) were compared to 18 controls (57 ± 9 years). Eight patients were tested before and after BTX treatment: baseline (week 0); 2 weeks later (week 2), at week 4 BTX injection followed the testing. Further evaluation included 2 weeks (week 6) and 4 weeks (week 8) after the injection. Controls were investigated twice. Forearm and hand were fixed in a splint. The force sensor (FORT 1000, World Precision Instruments) was connected via amplifier with CED Power 1401, and the applied force displayed as a time dependant curve. Force levels were calculated (20%, 40%, 60%, 80%) in relation to maximum force. Subjects pressed the index finger on the force sensor according to a given line. The line consisted of five horizontal plateaus alternating with ascending ramps, and included the increasing force levels. Square root means of each plateau/ramp were calculated separately (Signal Software 4.02). Results: Force regulation in five horizontal plateaus differed between the two groups at Plateau 1: p = 0.02; Plateau 2: p = 0.03; Plateau 3:

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p = 0.06. Differences of force regulation in four ascending ramps occurred for Ramp 1: p = 0.04; Ramp 2: p = 0.07; Ramp 3: p = 0.05. In patients, ANOVA revealed a time effect for horizontal plateaus (p = 0.04), a trend in ascending ramps (p = 0.054) and a ramp  time interaction (p = 0.04). Plateau 1 decreased between week 0 to 6 (p = 0.05) and 0 to 8 (p = 0.045). Plateau 2 changed from weeks 2 to 6 (p = 0.03); week 4 to week 6 (p = 0,02). Ramp 1 changed from week 0 to 4 (p = 0.051) and week 0 to 8 (p = 0.04); for Ramp 2, 3, 4 a trend occurred before and after BTX treatment. Controls remained unchanged. Conclusion: Differences in force regulation between patients and controls affected regulation with minimal force. BTX treatment might have an effect on force control that involves minimal strength and therefore improve sensorimotor integration. doi:10.1016/j.baga.2011.01.080

P161 Localization of deep brain electrodes correlates with clinical efficacy of pallidal deep brain stimulation in cervical dystonia T. Schönecker, A. Kühn, D. Gruber, A. Kivi, E. Lobsien, G.-H. Schneider, K.-T. Hoffmann, A. Kupsch (Berlin, Leipzig) Objective: Deep brain stimulation (DBS) of the Globus Pallidum internus (GPi) improves cervical dystonia. To which extend this improvement is influenced by the anatomical localization of the deep brain electrode within a specific subarea of the GPi is unclear. Methods: Relative clinical improvement (CI in %) of the severity score of Toronto Western Spasmodic Torticollis Rating Scale was assessed following DBS at different pallidal localizations in 12 patients with cervical dystonia and 7 patients with segmental dystonia with a predominant cervical involvement (median age 56; 9 male). Localizations of contacts were derived from postoperative MRI-data following anatomical normalization into the standard Montreal Neurological Institute (MNI) stereotactic space. All patients underwent four sessions of test stimulation of at least 24 h with activation of different contacts of the DBS-electrode. CIs were mapped to stereotactic coordinates of the corresponding bilateral active contacts. Contacts were clustered according to the stimulation-induced CI (low CI < 30%, intermediate CI > 30% but <60%, or high CI P 60%). Results: Anatomical Euclidean distances of active contacts with respect to the geometrical center (centroid) of the assigned cluster differed between clusters (p < 0.001). Euclidean distances of contacts with respect to the centroid of the cluster inducing high CIs (HCIcentroid) correlated to the degree of CI (left: Rho = 0.66; p < 0.0001; right: Rho = 0.63; p < 0.0001) and followed an exponential regression curve (R2 = 0.499). Stereotactical coordinates of HCIcentroids were located to MNI: X: 20.35 mm, Y: 7.10 mm, Z: 6.09 mm on the left side and to MNI: X: 20.94 mm, Y: 6.80 mm, Z: 5.64 mm on the right side. Conclusion: The clinical effectiveness of pallidal DBS on cervical dystonia decreases over anatomical distance to a specific sub-region of the posteroventrolateral GPi. The results may facilitate post-operative selection of contacts most proximal to the optimal subregion of stimulation and may optimize postoperative clinical testing. doi:10.1016/j.baga.2011.01.081

P162 Alien hand syndrome: Neural correlates of movements without conscious will I. Galazky, H.-J. Heinze, M. Schaefer (Magdeburg) Background: The alien hand syndrome is a striking phenomenon characterized by purposeful and autonomous movements that are

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Abstract / Basal Ganglia 1 (2011) 13–45

not voluntarily initiated. This study aimed to examine neural correlates of this rare neurological disorder in a patient with corticobasal degeneration and alien hand syndrome of the left hand. Methodology/principal findings: We employed fMRI to investigate brain responses associated with unwanted movements in a case study. Results revealed that alien hand movements involved a network of brain activations including the primary motor cortex, premotor cortex, precuneus, and right inferior frontal gyrus. Conscious and voluntary movements of the alien hand elicited a similar network of brain responses but lacked an activation of the inferior frontal gyrus (IFG). The results demonstrate that alien and unwanted movements may engage similar brain networks than voluntary movements, but also imply different functional contributions of prefrontal areas. Since the inferior frontal gyrus was uniquely activated during alien movements, the results provide further support for a specific role of this brain region in inhibitory control over involuntary motor responses. Conclusions/significance: We discuss the outcome of this study as providing evidence for a distributed neural network associated with unwanted movements in alien hand syndrome, including brain regions known to be related to movement execution and planning as well as areas that have been linked to inhibition control (IFG) and experience of agency (precuneus). doi:10.1016/j.baga.2011.01.082

POSTER SESSION 2.5 Basic science P163 Glucocerebrosidase deficiency and dopaminergic cell death: Relevance to Parkinson disease D. Alvarez-Fischer, C. Noelker, L. Lu, A. Sturn, R. Roscher, E.C. Hirsch, W.H. Oertel, A. Hartmann (Marburg; Paris, FR; Allschwil, CH) Gaucher disease (GD) is an autosomal recessive disease, caused by a lack or functional deficiency of the lysosomal enzyme, glucocerebrosidase (GBA), which catalyses the breakdown of glucocerebroside, to glucose and ceramide (Butler and Grabowski, 2001). Recently, mutations in the glucerebrosidase gene have been associated with Parkinson disease (PD). PD is a common neurodegenerative disorder characterized clinically by akinesia, rigidity and rest tremor (Fahn, 2000). The cardinal neuroanatomical feature of PD is a massive and preferential loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in a drastic decline in striatal dopamine concentrations. In a large multicenter study, 3% with PD, so far classified as ‘idiopathic’, displayed the frequent N370S and L444P GBA mutations (Sidransky et al., 2009). When taking into consideration rarer mutations, this figure has been estimated to rise to 7%. Moreover, this association appears not be restricted to Ashkenazi Jews as initially suggested (Aharon-Peretz et al., 2004) but is present world wide in a multitude of ethnicities. Thus, GBA mutations can be considered the most important genetic vulnerability factor for PD identified to date (DePaolo et al., 2009). Surprisingly, little is known how GBA mutations may contribute to dopaminergic cell death, the major cellular alteration in PD. In the present, proof of concept study, we have investigated (i) in vitro whether a decrease to GBA activity may render dopaminergic neurons susceptible to MPP+ (1-methyl-4-phenylpyridinium) and (ii) in vivo whether inhibition of the enzyme glucosylceramide synthase (a glucosyl transferase enzyme responsible for the first step in the synthesis of most glycosphingolipids, including glucosylceramide)

may protect mice tetrahydropyridine).

against

MPTP

(1-methyl-4-phenyl-1,2,3,6-

doi:10.1016/j.baga.2011.01.083

P164 Optimal motor learning strategy in the neurorehabilitation P. Kiriazov (Sofia, BG) Motivation: Parkinson’s disease (PD) may significantly affect the control of voluntary movements that normally are performed automatically and optimally as regards motion speed, position accuracy, and energy loss. In case of PD, control functions (neural signals to muscles) have to be re-learnt and optimised. Recent research has shown that voluntary exercises can increase levels of brain-derived neurotrophic factor and other growth factors, stimulate neurogenesis, and improve brain plasticity and motor learning performance. Methods: Our motor learning strategy for goal-directed motion tasks is based on underlying principles of movement neuroscience, optimal control theory, and dynamics of human motion. Optimal control functions in fast voluntary movements have a triphasic shape: burstpause-burst. The following basic parameters are to be learnt: the magnitude and relative timing of the neural signals to the joint muscles. The neural structures that compute the required muscle excitation parameters are the so-called internal models and the proposed approach can be used to rebuild such models (cortical reorganization). We have developed methods for optimal motor learning in three important tasks: reaching, sit-to-stand-up, and performing steps. Results: Our motor learning approach was applied on realistic mathematical models and healthy subjects so far. The models make it possible first to specify the control magnitudes (burst levels), which are appropriate for the corresponding motion task to be performed. Then, we applied our trial-and-correction algorithm to learn the timing sequence parameters. By computer simulation, we verified that the learning parameters converge and the number of trials is very small. In addition, practical experiments with single-joint, rapid aiming movements of the arm confirm the feasibility and efficacy of the proposed approach. As in the successful Lee Silverman Voice Treatment, we can apply principles of decomposition and graduality to learn any complex, multijoint motion task. Conclusion: We propose optimal motor learning strategy and can develop an efficient training methodology for PD-patients. It will definitely help them re-learn and perform various motion tasks in their daily life activities. Our methodology can also be very useful when applying functional electrical stimulation because optimising the magnitude of the electrical signals and the timing sequence for stimulating the muscles is a very important issue. doi:10.1016/j.baga.2011.01.084

P165 Effects of IGF-1 on differentiation and expansion of long term expanded fetal murine neural stem cells J. Buddensiek, T. Ehle, A. Hermann, A. Storch, M. Sabolek (Greifswald, Dresden, Schwendi) Background: Insulin-like growth factor-1 (IGF-1) is a circulating peptide hormone and trophic factor, playing an important role in development and maintenance of cellular integrity in different tissues, including the central nervous system. In recent years, several studies reported an antiapoptotic effect of IGF-1 on different cell types including neuronal cells. Meanwhile, latest findings demonstrate