TMS on the dorsolateral prefrontal cortex induces striatal dopamine release. A 18F-DMFP PET study.
Poster No:
53
Submission Type:
Abstract Submission
Authors:
usman jawed shaikh1, Antonello Pellicano2, Andre Schüppen1, Alexander Heinzel3,4, oliver winz3, Hans Herzog4, felix Mottaghy3,5, Ferdinand Binkofski1,4
Institutions:
1Section Clinical Cognitive Sciences, Department of Neurology, RWTH Uniklinik Aachen, Aachen, Germany, 2Department of Educational Sciences, University of Catania, Catania, Catania, 3Department of Nuclear Medicine, RWTH Uniklinik Aachen, Aachen, Germany, 4Research Centre Juelich, Institute of Neuroscience and Medicine (INM-4), Jülich, Germany, 5Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht, Netherlands
First Author:
usman jawed shaikh
Section Clinical Cognitive Sciences, Department of Neurology, RWTH Uniklinik Aachen
Aachen, Germany
Section Clinical Cognitive Sciences, Department of Neurology, RWTH Uniklinik Aachen
Aachen, Germany
Co-Author(s):
Andre Schüppen
Section Clinical Cognitive Sciences, Department of Neurology, RWTH Uniklinik Aachen
Aachen, Germany
Section Clinical Cognitive Sciences, Department of Neurology, RWTH Uniklinik Aachen
Aachen, Germany
Alexander Heinzel
Department of Nuclear Medicine, RWTH Uniklinik Aachen|Research Centre Juelich, Institute of Neuroscience and Medicine (INM-4)
Aachen, Germany|Jülich, Germany
Department of Nuclear Medicine, RWTH Uniklinik Aachen|Research Centre Juelich, Institute of Neuroscience and Medicine (INM-4)
Aachen, Germany|Jülich, Germany
felix Mottaghy
Department of Nuclear Medicine, RWTH Uniklinik Aachen|Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+)
Aachen, Germany|Maastricht, Netherlands
Department of Nuclear Medicine, RWTH Uniklinik Aachen|Department of Radiology and Nuclear Medicine, Maastricht University Medical Center (MUMC+)
Aachen, Germany|Maastricht, Netherlands
Ferdinand Binkofski
Section Clinical Cognitive Sciences, Department of Neurology, RWTH Uniklinik Aachen|Research Centre Juelich, Institute of Neuroscience and Medicine (INM-4)
Aachen, Germany|Jülich, Germany
Section Clinical Cognitive Sciences, Department of Neurology, RWTH Uniklinik Aachen|Research Centre Juelich, Institute of Neuroscience and Medicine (INM-4)
Aachen, Germany|Jülich, Germany
Introduction:
Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique which can modulate connectivity in the human brain. It is commonly used for depression treatments with long stimulation protocols to the Pre Frontal Cortex (PFC). In this multi-modal study, We combined Positron Emission Tomography (PET) and TMS technique to investigate the fronto-striatal connectivity in the human brain. Fronto-striatal networks are responsible for a wide range of motor and cognitive functions that includes emotion regulation, movement and attention.
In PET sessions, we measured the release of endogenous dopamine in the striatum in response to repeated blocks of excitatory, intermittent theta burst stimulation (iTBS) of the Left-Dorsolateral Prefrontal Cortex (L-DLPFC). The 18F-DesmethoxyFallypride (DMFP) radioligand was utilzed, as it is a high affinity Dopamine receptor-antagonist which binds to the D2,D3 receptors in striatum region..
The radioligand has benefits, including longer physical half-life and its transportation through off-site cyclotron unit, thus accomplishing the demand of pharmacologic challenging studies.The main objective of the current study was to test the dose dependent effects of iTBS over the left DLPFC on the dopamine release in the striatum.
In PET sessions, we measured the release of endogenous dopamine in the striatum in response to repeated blocks of excitatory, intermittent theta burst stimulation (iTBS) of the Left-Dorsolateral Prefrontal Cortex (L-DLPFC). The 18F-DesmethoxyFallypride (DMFP) radioligand was utilzed, as it is a high affinity Dopamine receptor-antagonist which binds to the D2,D3 receptors in striatum region..
The radioligand has benefits, including longer physical half-life and its transportation through off-site cyclotron unit, thus accomplishing the demand of pharmacologic challenging studies.The main objective of the current study was to test the dose dependent effects of iTBS over the left DLPFC on the dopamine release in the striatum.
Methods:
23 healthy subjects participated in the study, who underwent iTBS sham (control) and verum (active) stimulations on separate days.The stimulation intensity was set at 90% of resting motor threshold (rMT) for the verum (active) condition. In both stimulation session, the total duration of the PET scan was 120 mins (28 time frames), consisting of 4 excitatory iTBS delivered to the left-DLPFC at 30 mins interval.
Excitatory iTBS protocol was comprised of 600 pulses, delivered in a sequence of 20 trains and 10 theta-bursts in a total duration of 190 secs. Each 2 secs long train consisted of a burst of 3 stimuli at 50 Hz, repeated in 5 Hz frequency and having inter-train interval of 8 secs
The repeated TMS inside the PET scanner were performed using neuro-navigation. 18F-DMFP was used as the radiotracer, which allowed us to perform measurements lasting 120 minutes. PET dynamic data was analysed using reference method in which cerebellum was used as the reference region (due to lack of D2-D3receptors). Ratio of the striatal and cerebellar activities were calculated at different time points for sham and verum conditions and termed as indices to the receptor binding. Receptor Binding ratios were the main outcome measure representing the ligand binding which is inversely proportional to the Dopamine (DA) levels. Mean Binding ratios in the sub-regions of the striatum (Nucleus Caudate and Putamen) were compared between the two conditions using repeated measures of analysis of variance (ANOVA).
Excitatory iTBS protocol was comprised of 600 pulses, delivered in a sequence of 20 trains and 10 theta-bursts in a total duration of 190 secs. Each 2 secs long train consisted of a burst of 3 stimuli at 50 Hz, repeated in 5 Hz frequency and having inter-train interval of 8 secs
The repeated TMS inside the PET scanner were performed using neuro-navigation. 18F-DMFP was used as the radiotracer, which allowed us to perform measurements lasting 120 minutes. PET dynamic data was analysed using reference method in which cerebellum was used as the reference region (due to lack of D2-D3receptors). Ratio of the striatal and cerebellar activities were calculated at different time points for sham and verum conditions and termed as indices to the receptor binding. Receptor Binding ratios were the main outcome measure representing the ligand binding which is inversely proportional to the Dopamine (DA) levels. Mean Binding ratios in the sub-regions of the striatum (Nucleus Caudate and Putamen) were compared between the two conditions using repeated measures of analysis of variance (ANOVA).
Results:
Mean receptor Binding ratios showed a significant difference between sham and verum stimulations. We observed lower Binding ratios in the verum stimulation compared to sham stimulation. Verum iTBS increased the dopamine release in both striatal sub-regions, relative to sham iTBS. Dopamine levels in the verum stimulation session increased progressively across the time frames within about 75 minutes (after three doses of iTBS stimulation) and then essentially remained unchanged until the end of the session.
Conclusions:
Results suggest that the short-timed iTBS protocol performed in time-spaced blocks can effectively induce a dynamic dose dependent increase dopaminergic fronto-striatal connectivity. This scheme could represent a valuable alternative to painful, long stimulation protocols in experimental and therapeutic settings. Specifically, our results demonstrate that three repeated iTBS, spaced by a short time period, achieve larger effects than one single stimulation. This finding has implications for the planning of therapeutic interventions, for example, for the treatment of major depression.
Brain Stimulation:
Non-invasive Magnetic/TMS 1
TMS
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
PET Modeling and Analysis 2
Keywords:
Data analysis
Dopamine
Positron Emission Tomography (PET)
Transcranial Magnetic Stimulation (TMS)
1|2Indicates the priority used for review
Provide references using author date format
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