Projects / Programmes source: ARIS


Research activity

Code Science Field Subfield
3.03.00  Medical sciences  Neurobiology   

Code Science Field
B640  Biomedical sciences  Neurology, neuropsychology, neurophysiology 

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
dystonia, zolpidem, GABA, 18F-Flumazenil/PET, FDG/PET, transcranial magnetic stimulation, TMS
Evaluation (rules)
source: COBISS
Researchers (21)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  33621  PhD Jurij Bon  Psychiatry  Researcher  2016 - 2018  162 
2.  34774  PhD Gregor Brecl Jakob  Neurobiology  Researcher  2016 - 2018  69 
3.  24999  PhD Boštjan Frelih  Mathematics  Researcher  2016  14 
4.  30915  PhD Dejan Georgiev  Neurobiology  Researcher  2016 - 2018  189 
5.  28624  PhD Milica Gregorič Kramberger  Neurobiology  Researcher  2016 - 2018  223 
6.  11714  PhD Marko Grmek  Cardiovascular system  Researcher  2016 - 2018  161 
7.  33876  Luka Jensterle  Cardiovascular system  Technical associate  2016 - 2018  42 
8.  30072  PhD Maja Kojović  Neurobiology  Head  2016 - 2018  127 
9.  23364  PhD Petra Kolenc  Pharmacy  Researcher  2016 - 2018  136 
10.  08095  PhD Mojca Kržan  Neurobiology  Researcher  2017 - 2018  268 
11.  22346  PhD Luka Ležaič  Human reproduction  Researcher  2016 - 2018  236 
12.  39010  Ruben Perellon Alfonso  Neurobiology  Researcher  2016 - 2018 
13.  05380  PhD Zvezdan Pirtošek  Neurobiology  Researcher  2016 - 2018  734 
14.  37994  Katja Romarić    Technical associate  2017 - 2018  15 
15.  21495  PhD Nejc Šarabon  Sport  Researcher  2016 - 2018  914 
16.  07002  PhD Dušan Šuput  Neurobiology  Researcher  2017 - 2018  433 
17.  24691  PhD Petra Tomše  Cardiovascular system  Technical associate  2016 - 2018  122 
18.  15442  PhD Maja Trošt  Neurobiology  Researcher  2016 - 2018  451 
19.  50225  Katarina Vogelnik  Medical sciences  Researcher  2017 - 2018  16 
20.  26268  PhD Andrej Vovk  Neurobiology  Researcher  2017 - 2018  52 
21.  20484  PhD Katja Zaletel  Metabolic and hormonal disorders  Researcher  2016 - 2018  415 
Organisations (3)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  75,513 
2.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  45,384 
3.  1669  University of Primorska, Andrej Marušič Insitute  Koper  1810014007  10,501 
Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal repetitive movements and postures of affected parts of the body (Albanese et al. , 2013). The present view of dystonia is as of a circuit disorder, involving basal ganglia-thalamo-cortical and cerebello-thalamo-cortical pathways(Lehericy et al. , 2013). One of the key pathophysiological features of dystonia is decreased inhibition at the several level of central nervous system. (Quartarone and Hallett, 2013, Hallett, 2011). The lack of inhibition may account for many of the dystonic symptoms, such as co-contraction of antagonistic muscles, loss of selectivity in muscle activation during movement or overflow of dystonic symptoms in body parts not engaged in the movement. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the CNS. Studies in animal models, as well as neuroimaging and electrophysiological data on dystonic patients provide evidence of abnormal GABA neurotransmission in dystonia (Hallett, 2011, Gernert et al. , 2000, Levy and Hallett, 2002, Garibotto et al. , 2011, Ridding et al. , 1995). Currently, there is no cure for dystonia, but there are several symptomatic treatment options, including medications and surgical approaches (Thenganatt and Jankovic, 2014). While only minority of dystonia patients is eligible for deep brain stimulation (Krauss, 2002), most affected individuals are depended on pharmacological treatments for symptomatic relieve. These include botulinum toxin injections and oral medications(Thenganatt and Jankovic, 2014). Botulinum toxin injections treatment is effective in focal and segmental dystonia, but it requires repeated injections, may be associated with resistance to treatment and is expensive. Available oral medications are however not very effective (particularly in adult dystonia patients) and may be associated with intolerable adverse effects(Balash and Giladi, 2004). Therefore, research into the use of new pharmaceuticals approaches is warranted. Zolpidem is a widely used hypnotic agent that potentiates GABA transmission, as a selective agonist of the benzodiazepine subtype receptor α-1(Depoortere et al. , 1986). Zolpidem has been recently reported in an open- labelled study to be effective in primary focal and generalized dystonia, with the effect being variable among different dystonia patients(Miyazaki et al. , 2012). The success of zolpidem in relieving dystonic symptoms might be related to the high density of zolpidem binding receptors in the output nuclei of basal ganglia and in the cerebellum, the structures involved in the pathophysiology of dystonia(Dennis et al. , 1988, Mink, 2003, Vitek, 2002). The aims of our study are to investigate the clinical effectiveness of zolpidem in a double bling manner and to investigate the metabolic and electrophysiological correlated of zolpidem effect in different forms of primary focal dystonias. We hypothesise that responsiveness to zolpidem relates to inter-individual differences in distribution and amount of α-1 receptors in the structures involved in the pathophysiology of dystonia. We will study (i) the clinical effect of zolpidem (ii) the effect of zolpidem on global brain metabolism using FDG/PET, (iii) the binding distribution of zolpidem on GABA- A receptor complex using 18F-Flumazenil/PET and (iv) zolpidem effect on electrophysiological measures of GABA-A intracortical inhibition, using transcranial magnetic stimulation.
Significance for science
The proposed study combines two modern methods, namely PET brain imaging and transcranial magnetic stimulation in studying the pathophysiology of neurological diseases and the mechanism of response to treatment. The present study is relevant for several reasons. Focal dystonia is a common movement disorders, which significantly contributes to overall disability and reduced quality of life of the patients. Botulinum toxin is the treatment of choice but primary or secondary non-responders are rather common. Current treatment with oral medication is unsatisfactory and commonly associated with side effects. Novel therapeutic approaches are being searched for. In this context it is important to develop neuroimaging end electrophysiological predictors of response to medications, which would help clinicians to better manage focal dystonia patients. . If the results of our study are as we predict, zolpidem could become a treatment of choice in dystonia. This is particularly important given the fact that there is currently no effective oral therapy for dystonia. Finally, investigation of possible relationship between distribution of GABA receptors and electrophysiological measures of intracortical inhibition may provide novel information in the pathophysiological of dystonia.
Significance for the country
Previous studies in dystonia have shown that among patient there is a clear movement away from full-time employment to part-time and from all forms of employment to early retirement due to ill health. There is some indication that improvements in treatment therapies may change this trend (Butler et al. , 1998). Thus new effective therapy may directly result in significant number of subjects remaining in work and consequently using less state benefits. By ameliorating dystonic symptoms zolpidem may improve how the patient is coping with the various personal, social, and family issues caused by the onset and potential gradual and this may have indirect benefit for society.
Most important scientific results Interim report, final report
Most important socioeconomically and culturally relevant results Interim report, final report
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