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42. A neuronal NO synthase promoter polymorphism modifies ACC functioning in healthy controls and schizophrenia

42. A neuronal NO synthase promoter polymorphism modifies ACC functioning in healthy controls and schizophrenia

e20 Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88 Jülich, Institut für Neurowissenschaften und Biophysik (INB 3), Jülich, Germany...

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Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88

Jülich, Institut für Neurowissenschaften und Biophysik (INB 3), Jülich, Germany, 2 Heinrich-Heine-Universität, Vogt Institut für Hirnforschung, Düsseldorf, Germany, 3 Max-Planck-Institut für neurologische Forschung, Köln, Germany, 4 Brain Imaging Center West (BICW), Jülich, Germany, 5 Medizinische Universität, Abteilung für palstische Chirurgie, Innsbruck, Austria) In this functional magnetic resonance imaging study, we examined changes in cortical activation and connectivity in two patients following unilateral heterotopic replantation of the hand and distal forearm to the upper arm for proximal forearm tumours. The patients and a group of healthy controls performed visually paced hand movements with their left, right, or both hands. Effective connectivity during this task was assessed among a bilateral motor network – comprising primary motor cortex (M1), lateral premotor cortex (PMC), and supplementary motor area (SMA) – using dynamic causal modelling. When moving the normal hand both patients showed inhibition of the ipsilateral PMC and SMA, indicating a suppression of inference by the hemisphere controlling the replanted hand on physiological motor execution. Moving the replantated hand both patients showed increased activation of the PMC contralateral to surgery (reflecting increased effort), and a pathological inhibition exerted by the ipsilateral M1 on its active contralateral homologue indicative of a disturbed modulation of the inhibitory M1–M1 balance. In one patient, M1 contralateral to surgery received increased tonic (intrinsic connectivity) and phasic (replantated hand movement) facilitating input, whereas in the other patient pathological suppression was present. These differences in connectivity correlated with a reduced behavioural performance of the latter patient as assessed by kinematic analysis. Moreover, the increased recruitment of the contralateral M1 and the concurrent superior behavioural outcome seem to be related to an earlier and more intense rehabilitation commenced in the first patient. This study demonstrates the potential of functional neuroimaging to monitor plastic changes of cortical connectivity between cortical motor areas due to peripheral nerve surgery and subsequent recovery in individual patients, which may provide a valuable tool to understand, evaluate and enhance motor rehabilitation. doi:10.1016/j.clinph.2008.07.040

40. Deep brain stimulation in the nucleus accumbens – outcomes after one year stimulation in patients with treatment resistant obsessive compulsive disorder—W. Huff, J. Kuhn, D. Lenartz, S.-H. Lee, J. Klosterkötter, V. Sturm (Universität zu Köln, Medizin/Psychiatrie, Köln, Germany) Background: The effects of deep brain stimulation (DBS) in patients with obsessive compulsive disorder (OCD) have been presented in several case reports, case series and even in two randomized sham controlled long-term observations. Predominantly bilateral stimulation of the anterior limb of the internal capsule was presented. Methods: Results of unilateral stimulation of the right Nucleus accumbens (NAC) after 12 months in 10 patients with severe treatment resistant OCD were reported. Results: Mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores decreased significantly from baseline to one-year follow-up. Five of ten patients showed a partial response (more than 25% decrease). One of them had a more than 35% decline in Y-BOCS severity indicating a full response. Depression, global functioning and quality of life improved within one year. Anxiety, global symptom severity and cognitive function showed no significant changes. In general, DBS was well tolerated.

Conclusions: DBS of the unilateral right NAC showed encouraging results after one year in patients with treatment resistant OCD. The effects are comparable with previous reports presenting bilateral stimulation of the internal capsule in treatment resistant OCD. doi:10.1016/j.clinph.2008.07.041

41. Limbic and fronto-cortical influence on the control of the maximum force—M. Al Qawasmeh 1, W. Hermann 1, P. Günther 2, P. Baum 2 (1 Paracelsus klinik, Neurologie, Zwickau, Germany, 2 Universität-Leipzig, Neurologie, Leipzig, Germany) Introduction: The muscular coordination of movement depends on the integrity of the cerebellar and basal ganglia loop. An optimal control and situation-adapted emotional readiness is a precondition for achieving the maximum power of the musculoskeletal system. Methods: In 100 healthy control volunteers (58 women, 42 men, median age 32 years), an isometric force measurement device (Isocheck, company Mechatronic) with six indicator movements was used. The test protocol included the following movements: upper arm abduction and adduction, lumbar flexion and extension and hip abduction and adduction. The maximum strength of the spontaneous movement and after 30 s concentration were determined. Results: All indicator movements showed an increase in maximum force to the previous concentration (Table 1). Table 1

Upper arm adduction Upper arm abduction Lumbar flexion Lumbar extension Hip adduction Hip abduction

Spontaneous maximum force [Nm]

Force to the maximum concentration [Nm]

% Increase in power

86.11 78.17 82.9 135.61 134,85 116.86

108.32 99.32 97.22 165.22 155.05 133.6

25.79 27.06 17.27 21.83 14.98 14.32

Conclusion: After previous concentration and emotional preparation, an increase in the maximum force could be observed. The anatomical correlation could be an intact striatale fronto-limbic train and a coupling of the amygdala to the basal ganglia. The power increase is based on an optimization of basal ganglionar control of the movement program. doi:10.1016/j.clinph.2008.07.042

42. A neuronal NO synthase promoter polymorphism modifies ACC functioning in healthy controls and schizophrenia—A. Reif 1, A.-C. Ehlis 1, C. Bähne 1, M. Schecklmann 1, C. Jacob 1, S. Herterich 2, K.-P. Lesch 1, A. Fallgatter 1 (1 Universität Würzburg, Klinik für Psychiatrie, Würzburg, Germany, 2 Universität Würzburg, Institut für klinische Biochemie und Pathobiochemie, Würzburg, Germany) Nitric oxide (NO), the second messenger of the NMDA receptor, is a gaseous neurotransmitter and interacts with both the dopaminergic and the serotonergic systems. Genetic and pharmacological studies in animals have demonstrated a role for the neuronal isoform of nitric oxide synthase (nNOS, NOS-I) in a wide range of behaviors. We have previously identified a repeat polymorphism in the promoter region of NOS1, termed NOS1 ex1f-VNTR, which controls gene expression and impacts on the neuronal transcriptome. By genotyping more than 5,000 individuals, we demonstrated that short vari-

Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88

ants of NOS1 ex1f-VNTR are associated with impulsive behaviors and disease severity in schizophrenia. To uncover the underlying neurobiological mechanisms, we have conducted a genomic imaging study on 48 patients suffering from schizophrenia and 167 healthy controls, all of which were genotyped for NOS1 ex1f-VNTR. All subjects were investigated by means of a Continuous Performance Test (CPT) with parallel EEG recording. The elicited event-related potentials were subsequently further analysed for their topography. In healthy controls, the NoGo centroid, a measure of medial prefrontal activity during response inhibition, was localized significantly more posterior in carriers of the short NOS1 Ex1f-VNTR allele (LL vs. SS, 3.1 ± 0.5 vs. 3.3 ± 0.5; p < 0.05). While not being significant (probably due to small sample size), the finding nominally remained the same in schizophrenia patients (LL vs. SS, 3.1 ± 0.7 vs. 3.3 ± 0.4) with patients carrying two short alleles displaying significantly decreased P300 NoGo amplitudes. Together, these data implicate hypo-activation of the anterior cingulate cortex (ACC), which is the major neural source for the specific topography of the NoGo centroid, in short allele carriers. This suggests impaired medial prefrontal functioning in these subjects, as compared to carriers of the long allele. As the ACC is known to be involved in the processing of emotion and reward in behavioral control, this might well underlie the observed behavioral consequences of short NOS1 Ex1f-VNTR variants (i.e., increased impulsivity). Furthermore, by impaired ACC activation short at-risk alleles might contribute to defective response control found in schizophrenic disorders. These findings provide a rationale how genetically determined disturbances in NO signaling might be linked to human psychopathology, namely via differential activation of prefrontal circuits.

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Fig. 1.

doi:10.1016/j.clinph.2008.07.043

43. The palpebral variety of blepharospasms – differentiation from apraxia of eyelid opening and from inhibition disorders via synchronous electromyographical recordings—A. Stenner 1,2, G. Reichel 1, W. Hermann 2 (1 Paracelsusklinik Zwickau, Kompetenzzentrum Bewegungsstörungen, Zwickau, Germany, 2 Paracelsusklinik Zwickau, Neurologische Abteilung, Zwickau, Germany) Introduction: Blepharospasm (BS) is one of the diseases, which can be treated easily and effectively with Botulinumtoxin (Btx) injections into the orbicularis oculi. The reason for primary failures in Btx-therapy almost always seems to be inaccurate classification of the three most important differential diagnoses: 1. palpebral variety of BS, 2. inhibition failures of the mm. orbicularis oculi et levator palpebrae superioris, 3. levator muscle apraxia. Differentiating these three disorders via electromyographical (EMG) recordings of eye muscles is the main objective of this investigation. Methods: After excluding other illnesses, six patients referred to us with the diagnosis ‘‘BS – primary therapy failure of Btx’’ were examined using synchronous EMG recordings (Fig. 1) of the m. levator palpebrae superioris and of the m. orbicularis oculi – pars palpebralis and pars orbitalis – at rest, and after the request to open and close their eyes (Fig. 2: recording at rest during spontaneous eye closing). Results: Four patients clearly showed the typical patterns of palpebral BS, whereas one patient suffered from apraxia of eyelid opening and another from inhibition failure. 1. The EMG of palpebral BS is characterized by continuous action potential patterns of motor units in the pars palpebralis and m. orbicularis oculi, irrespectively of intentional movements. Additionally, spontaneous potential groups in the m. orbicularis oculi

Fig. 2.

(involuntary lid movement) will also cause synchronous interruption of activity in the m. levator palpebrae, which is seen as a sign of intact reciprocal inhibition. Lid opening at request will cause dense activity patterns in the m. levator palpebrae superioris, which has only minor or no clinical eects. Furthermore, the innervation of the frontalis muscle can be observed clinically. 2. Disorders in the antagonism of the mm. levator palpebrae superioris et obicularis oculi will cause constant massive activity in both muscles. Additional spontaneous discharge groups in the m. orbicularis oculi (spontaneous lid movement) will not interrupt voluntary activity in the m. levator palpebrae superioris. 3. In apraxia of eyelid opening there will be no EMG activity, even if patients are requested to open their eyes. At rest both parts of the m. orbicularis oculi only show little or no activity. Spontaneous (lid movement) and involuntary innervation of this muscle will not show any special features. Summary: After primary therapy failure in Btx treatment of BS, differentiation between apraxia of eye lid opening, inhibition disorder and the palpebral variety of BS can be accomplished via EMG