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Repetitive transcranial magnetic stimulation of mid-dorsolateral frontal cortex induces release of dopamine in the striatum
Neurohnage
13, Number
6, 2001,
Part 2 of 2 Parts
ISE~lW PHYSIOLOGY
Repetitive transcranial magnetic stimulation of mid-dorsolateral frontal cortex inducesreleaseof dopamine in the striatum. A.P. Strafella, T. Paus, J. Barrett, A. Dagher Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada Introduction: Animal experiments have shown that descending pathways from the frontal cortex modulate the release of dopamine in subcortical areas such us the striatum. This modulation has been proposed to be an integral part of the pathophysiology of disorders associated with subcortical dopamine dysfunction such as schizophrenia, depression, and Parkinson’s disease. However, little is known about the anatomical pathways involved in the control of dopamine release in humans. Repetitive transcranial magnetic stimulation (rTMS) of the left mid-dorsolateral frontal cortex (MDL-FC) in humans has been reported to have a beneficial effect on depressive symptoms. The aim of the present study was to use positron emission tomography (PET) to determine whether rTMS of the left MDL-FC induces dopamine release in the striatum.
Methods: Eight normal volunteers underwent two PET scans with [ 1 lC]raclopride, one following rTMS of the left MDL-FC (X=-40, Y =32, Z=30) and one following rTMS of the control site in the left occipital cortex (OCC, X=-56, Y=-58, Z=-3). The scan order was randomized across subjects and ail scans were performed at the same time of day on two consecutive days for each individual. TMS was carried out with a Cadwell high-speed magnetic stimulator using a circular coil. The coil was held in a fixed position by a mechanical arm over the left MDL-FC or left OCC. Three rTMS blocks were delivered, each block separated by a 10 minutes interval; in each block, 15 lo-pulse trains of 1-set duration were delivered at a frequency of 10 Hz with an inter-tram interval of 10 sec. The stimuli were delivered at resting motor threshold over the 30 minutes prior to [ 1 lC]raclopride injection. PET data were acquired for 60 minutes after bolus tracer infusion. PET images were co-registered to each subject’s MRI and transformed into stereotaxic space. [ 1 lC]raclopride binding potential (BP) was calculated at each voxel, and a statistical parametric map of the change in binding was generated. A reduction in BP is assumed to reflect an increase in dopamine concentration.
Results: rTMS of the left MDL-FC cortex decreased [ 1 lC]raclopride BP only in the left dorsal caudate nucleus. The mean change in BP was -8.8% +/- 2.4 (F(1,7)=105, P
Diiussion: There are both direct (cortico-striatal) and indirect (cortico-nigral) of striatal dopamine release. We found that rTMS of the MDL-FC suggests that cortico-striatal fibres originating in the MDL-FC caudate nucleus.
anatomical connections thought to be involved in the modulation induces dopamine release in the ipsilateral caudate nucleus. This may promote local dopamine release in their target, the dorsal
51008
13, Number
6, 2001,
Part 2 of 2 Parts
ISE~lW PHYSIOLOGY
Repetitive transcranial magnetic stimulation of mid-dorsolateral frontal cortex inducesreleaseof dopamine in the striatum. A.P. Strafella, T. Paus, J. Barrett, A. Dagher Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada Introduction: Animal experiments have shown that descending pathways from the frontal cortex modulate the release of dopamine in subcortical areas such us the striatum. This modulation has been proposed to be an integral part of the pathophysiology of disorders associated with subcortical dopamine dysfunction such as schizophrenia, depression, and Parkinson’s disease. However, little is known about the anatomical pathways involved in the control of dopamine release in humans. Repetitive transcranial magnetic stimulation (rTMS) of the left mid-dorsolateral frontal cortex (MDL-FC) in humans has been reported to have a beneficial effect on depressive symptoms. The aim of the present study was to use positron emission tomography (PET) to determine whether rTMS of the left MDL-FC induces dopamine release in the striatum.
Methods: Eight normal volunteers underwent two PET scans with [ 1 lC]raclopride, one following rTMS of the left MDL-FC (X=-40, Y =32, Z=30) and one following rTMS of the control site in the left occipital cortex (OCC, X=-56, Y=-58, Z=-3). The scan order was randomized across subjects and ail scans were performed at the same time of day on two consecutive days for each individual. TMS was carried out with a Cadwell high-speed magnetic stimulator using a circular coil. The coil was held in a fixed position by a mechanical arm over the left MDL-FC or left OCC. Three rTMS blocks were delivered, each block separated by a 10 minutes interval; in each block, 15 lo-pulse trains of 1-set duration were delivered at a frequency of 10 Hz with an inter-tram interval of 10 sec. The stimuli were delivered at resting motor threshold over the 30 minutes prior to [ 1 lC]raclopride injection. PET data were acquired for 60 minutes after bolus tracer infusion. PET images were co-registered to each subject’s MRI and transformed into stereotaxic space. [ 1 lC]raclopride binding potential (BP) was calculated at each voxel, and a statistical parametric map of the change in binding was generated. A reduction in BP is assumed to reflect an increase in dopamine concentration.
Results: rTMS of the left MDL-FC cortex decreased [ 1 lC]raclopride BP only in the left dorsal caudate nucleus. The mean change in BP was -8.8% +/- 2.4 (F(1,7)=105, P
Diiussion: There are both direct (cortico-striatal) and indirect (cortico-nigral) of striatal dopamine release. We found that rTMS of the MDL-FC suggests that cortico-striatal fibres originating in the MDL-FC caudate nucleus.
anatomical connections thought to be involved in the modulation induces dopamine release in the ipsilateral caudate nucleus. This may promote local dopamine release in their target, the dorsal
51008