Changing Cerebral Blood Flow, Glucose Metabolism, and Dopamine Binding Through Transcranial Magnetic Stimulation: A Systematic Review of Transcranial Magnetic Stimulation-Positron Emission Tomography Literature

Abstract

Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation tool currently used as a treatment in multiple psychiatric and neurologic disorders. Despite its widespread use, we have an incomplete understanding of the way in which acute and chronic sessions of TMS affect various neural and vascular systems. This systematic review summarizes the state of our knowledge regarding the effects TMS may be having on cerebral blood flow, glucose metabolism, and neurotransmitter release. Forty-five studies were identified. Several key themes emerged: 1) TMS transiently increases cerebral blood flow in the area under the coil; 2) TMS to the prefrontal cortex increases glucose metabolism in the anterior cingulate cortex of patients with depression; and 3) TMS to the motor cortex and prefrontal cortex decreases dopamine receptor availability in the ipsilateral putamen and caudate respectively. There is, however, a paucity of literature regarding the effects TMS may have on other neurotransmitter and neuropeptide systems of interest, all of which may shed vital light on existing biologic mechanisms and future therapeutic development. SIGNIFICANCE STATEMENT: Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation tool currently used as a treatment in multiple psychiatric and neurologic disorders. This systematic review summarizes the state of our knowledge regarding the effects TMS on cerebral blood flow, glucose metabolism, and neurotransmitter release.

Fig. 1

Common experimental designs used in TMS-PET literature. Above is the representation of several different experimental designs used throughout the combined TMS and PET literature included in this review. These designs depict (A) studies examining CBF changes (measured with ¹⁵O-H₂O) induced by TMS using multiple short TMS-PET sessions, (B) single long session studies mainly used to investigate changes in dopamine receptor availability following TMS protocols, and (C) a standard longitudinal design that is primarily used to measure changes in glucose metabolism using [¹⁸F]Fluoro-2-deoxy-D-glucose PET.

Fig. 2

TMS transiently increases CBF at the site of stimulation. Above are representative models of electric fields following TMS to the motor (left) and dorsolateral prefrontal (right) cortices in standard space. Changes in rCBF were measured in vivo using PET scanning procedures via a [¹⁵O]H₂O radioligand. In seven published studies, 5 Hz and 1 Hz (low-frequency) TMS to the motor cortex transiently increased CBF at the site of stimulation. Six published studies suggested a transient increase in CBF at the site of stimulation using 20 Hz and 10 Hz (high-frequency) TMS to stimulate the DLPFC. Modeling parameters include a Magstim B70 coil at 60% machine output and standard tissue conductivity values. The electric fields depicted range from 70 to 120 millivolts.

Fig. 3

TMS to the motor cortex and the DLPFC influences dopamine receptor availability in a region-specific manner. Above are representative models of electric fields following TMS to the motor (top) and dorsolateral prefrontal (bottom) cortices in standard space. D2 dopamine receptor availability was measured in vivo using [¹¹C]raclopride, a radiotracer detectible through PET scanning procedures. Reported above are regions exhibiting a decrease in [¹¹C]raclopride binding in at least two publications. One study used [¹¹C]FLB 457. Overall, 5 Hz and 10 Hz TMS to the left motor cortex decreases [¹¹C]raclopride binding in the caudate (yellow) and putamen (red). 10 Hz TMS to the left dorsolateral prefrontal cortex (DLPFC) decreases [¹¹C]FLB 457 binding in the pregenual cingulate (orange) and orbitofrontal cortex (OFC) (purple). Additionally, 10 Hz TMS to the left DLPFC decreases [¹¹C]raclopride binding in the caudate (yellow) and putamen (red). Decreases in dopamine receptor availability suggest a TMS-induced dopamine release. Modeling parameters include a Magstim B70 coil at 60% machine output and standard tissue conductivity values. The electric fields depicted range from 70 to 120 millivolts.