Projects / Programmes source: ARIS

Influence of different neuronavigation procedures on treatment efficacy of repetitive transcranial magnetic stimulation in depression

Research activity

Code Science Field Subfield
3.09.00  Medical sciences  Psychiatry   

Code Science Field
B650  Biomedical sciences  Psychiatry, clinical psychology, psychosomatics 

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
transcranial magnetic stimulation, treatment-resistant depression, neuronavigation, brain connectivity, biomarkers
Evaluation (rules)
source: COBISS
Researchers (17)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  33621  PhD Jurij Bon  Psychiatry  Researcher  2016 - 2018  166 
2.  51786  PhD Mirjana Delić  Psychiatry  Researcher  2018  60 
3.  26484  PhD Andrej Kastrin  Medical sciences  Researcher  2017  148 
4.  30072  PhD Maja Kojović  Neurobiology  Researcher  2016 - 2018  131 
5.  12481  PhD Blanka Kores Plesničar  Psychiatry  Researcher  2016 - 2018  398 
6.  21239  PhD Blaž Koritnik  Medical sciences  Researcher  2016 - 2018  275 
7.  39409  Nejc Nadižar    Technical associate  2018  30 
8.  20415  PhD Brigita Novak Šarotar  Psychiatry  Researcher  2016 - 2018  158 
9.  37430  PhD Vida Ana Politakis  Psychology  Junior researcher  2018  27 
10.  18323  PhD Peter Pregelj  Psychiatry  Head  2016 - 2018  363 
11.  17893  PhD Grega Repovš  Psychology  Researcher  2016 - 2018  490 
12.  36162  PhD Anka Slana Ozimič  Neurobiology  Researcher  2016 - 2018  126 
13.  33735  PhD Neja Šamec  Biochemistry and molecular biology  Technical associate  2017  82 
14.  51785  PhD Nuša Šegrec  Psychiatry  Researcher  2018  205 
15.  22235  PhD Borut Škodlar  Psychiatry  Researcher  2016 - 2018  514 
16.  27742  PhD Alja Videtič Paska  Medical sciences  Researcher  2016 - 2018  219 
17.  05379  PhD Bojan Zalar  Medical sciences  Researcher  2016 - 2018  175 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,422 
2.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,215 
3.  0581  University of Ljubljana, Faculty of Arts  Ljubljana  1627058  97,913 
4.  1620  University Psyhiatric Hospital  Ljubljana - Polje  1191004000  3,459 
Affective disorders represent the largest share of the brain disorders related burden in European societies. During their treatment for a major depressive disorder (MDD), many patients fail to achieve remission. Continued symptoms of depression are related to functional impairment, increased use of health resources, increased overall mortality and greater risk of suicide. The prevalence of such treatment-resistant depression (TRD) ranges from 10% to 60% of all depressed patients, depending on the exact definition of TRD. Many new medications were developed for depression but have so far failed to show improved efficacy over standard treatment. Most promising alternative approach to treatment is the focal brain stimulation, which includes transcranial magnetic stimulation (TMS). TMS is a noninvasive neurophysiological procedure, which inhibits or excitates small areas of brain cortex under the TMS coil. Repetitive TMS protocols show moderately strong effect sizes but relatively low absolute response rates in patients with TRD. Theta burst stimulation (TBS) is one of the newest rTMS protocols, which is shorter, simpler, safer and more tolerable for patients. Recently it was shown that its efficacy is on par with classic rTMS stimulatory protocols for depression. Because efficacy depends also on the particular site of stimulation, neuronavigation procedures are used in the TMS treatment of depression to determine appropriate target stimulation site on the scalp. The standard procedure is to use the individual's structural magnetic resonance (MRI) scan to determine the location of an anatomical atlas based coordinate in dorsolateral prefrontal cortex. The usability of cortical stimulation targets determined in this way is questionable, firstly because of the natural variability of cortex anatomy and secondly because we can also expect variability due to pathological changes in networks involved in depression. As an alternative option it was recently proposed to use resting state functional connectivity MRI (rs-fcMRI) to determine the exact structure of functionally separate resting state networks in the brain of a individual patient in order to improve TMS target location adequacy. Our overall goal in this study is to investigate factors that would enable improvement in safety, simplicity and efficacy of present rTMS treatment protocols in individual patients with depression. We will use a combination of stimulatory and inhibitory TBS treatment protocols and try to determine in a clinical setting of a randomised study, whether the more complex resting state networks method translates into better treatment outcomes. Additionally we intend to investigate the influence of other possible sources of variability between groups by measuring known and predicted factors that could be related to medication and TMS antidepressant treatment efficacy. We will evaluate the presence of clinical treatment refractoriness variables, molecular biomarkers and quantitative electroencephalography and TMS markers that were shown to be related with depression treatment outcomes or more generally with the brain neuroplasticity. MRI scanning will be performed in order to enable TMS target location determination, but MRI data will also be used to analyse brain local and distributed network architecture (functional connectivity through rs-fcMRI methods and structural connectivity through diffusion tensor imaging). All procedures will be repeated after the end of treatment to determine possible changes within individual subjects and between both treatment groups. Besides its direct clinical value, the proposed project would also provide insights into neurophysiological mechanisms of depression and antidepressant treatment resistance, and make a contribution towards bridging the gap between molecular, cellular and systems understanding of brain function.
Significance for science
The proposed project builds on the state-of-the-art in the field of depression biomarkers, focal brain stimulation, and functional and structural connectivity. It extends and combines advancements in these fields in furthering understanding of the integration of brain function underlying affective processes, their interactions with cognitive control processes and their changes in psychopathological conditions such as major depression and its subtype of treatment-resistant depression. Contingent upon the successful funding and completion of the project we expect several significant methodological, theoretical and practical contributions to the development of science in relevant fields of research. First, the project will contribute to the development and testing of a novel approach for individual target localisation in TMS treatment. So far, there are only proof of concept studies on this question and if it turns out that the alternative resting state network localisation method translates into better treatment outcomes, this would represent a major step forward regarding TMS treatment   efficacy. Second, the project will help refine and develop analytical methods in the field of brain imaging research. Specifically, the project would contribute to a development of methods for reliable analysis of functional connectivity of resting state fMRI data on an individual subject’s level. Third, the project will help determine the value of newer cognitive neuroscience techniques for prediction of treatment resistance in TMS treatment of depression. The best new predictors will be incorporated with known predictors of treatment resistance into a new integrative biomarker method in hope of improving overall sensitivity and specificity of prediction. Fourth, the project will help to reconceptualise, study and understand changes in affective processes and their interaction with cognitive control processes  from the perspective of changed network dynamics in depression. Fifth, the project will test specific hypotheses about the role of molecular biomarkers in understanding mechanisms of neuroplasticity after focal brain stimulation in depression. This will in turn provide better understanding of translational aspects of dysfunction of brain circuits in depression and possibly enable novel approaches in its diagnosis and treatment.
Significance for the country
The research project will enable us to proceed with systematic research and evaluation of alternative treatments of patients with treatment-resistant depression. In terms of a wider health-related impact to the economy and society, it needs to be considered that affective disorders represent the single biggest source of direct and indirect brain disorders related costs in the EU. We assume that results will help improve current treatment options for depression and would therefore be in line with guidelines of Slovenian National Healthcare Plan and EU Health Strategy, which stress the importance of improving treatment of mental disorders, reducing the number of suicides in Slovenia and improving the quality of patients' lives. We expect to improve all three major health related factors in treated patients : prolongation of life expectancy, quality of life and personal satisfaction. By using the biomarker approach and analysing differences between neuronavigation procedures we will help improve the understanding of treatment resistance and general brain function in patients with depression before and after the rTMS treatment. Together with the improvement of patient’s quality of life we will improve the impact of the depression related economical burden for the society and estimate the cost-benefit ratio of specific proposed techniques for TMS treatment of depression. This economic benefit will remain as the best treatment practices identified are introduced into regular clinical practice and will also ve incorporated in the economic value of domestic medical expertise. Procedures developed in the project have a potential for commercial development of routinely used clinical tools.
Most important scientific results Interim report, final report
Most important socioeconomically and culturally relevant results Interim report, final report
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