Functional MRI reveals frequency-dependent responses during deep brain stimulation at the subthalamic nucleus or internal globus pallidus

• Published in: NeuroImage (Orlando, Fla.) Vol. 84; pp. 11 - 18
• Main Authors: Lai, Hsin-Yi, Younce, John R., Albaugh, Daniel L., Kao, Yu-Chieh Jill, Shih, Yen-Yu Ian
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-01-2014; Elsevier; Elsevier Limited
• Subjects: Animals; Biological and medical sciences; Brain; Brain mapping; Brain Waves - physiology; Connectome - methods; Deep brain stimulation; Deep Brain Stimulation - methods; Electrodes; fMRI; Functional connectivity; Fundamental and applied biological sciences. Psychology; Globus Pallidus - physiology; Internal globus pallidus; Laboratory animals; Magnetic Resonance Imaging - methods; Male; Motor Cortex - physiology; Nerve Net - physiology; NMR; Nuclear magnetic resonance; Parkinson's disease; Rat; Rats; Rats, Sprague-Dawley; Rodents; Studies; Subthalamic nucleus; Subthalamic Nucleus - physiology; Vertebrates: nervous system and sense organs; Functional connectivity; fMRI; Internal globus pallidus; Subthalamic nucleus; Rat; Deep brain stimulation; Rodentia; Central nervous system; Basal ganglion; Nuclear magnetic resonance imaging; Pallidum; Encephalon; Vertebrata; Mammalia; Animal; Functional imaging
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2013.08.026

Deep brain stimulation (DBS) represents a widely used therapeutic tool for the symptomatic treatment of movement disorders, most commonly Parkinson's disease (PD). High frequency stimulation at both the subthalamic nucleus (STN) and internal globus pallidus (GPi) has been used with great success for the symptomatic treatment of PD, although the therapeutic mechanisms of action remain elusive. To better understand how DBS at these target sites modulates neural circuitry, the present study used functional blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to map global brain responses to DBS at the STN and GPi of the rat. Robust activation centered in the ipsilateral motor cortex was observed during high frequency stimulation at either target site, with peak responses observed at a stimulation frequency of 100Hz. Of note, frequency tuning curves were generated, demonstrating that cortical activation was maximal at clinically-relevant stimulation frequencies. Divergent responses to stimulation were noted in the contralateral hemisphere, with strong cortical and striatal negative BOLD signal during stimulation of the GPi, but not STN. The frequency-dependence of the observed motor cortex activation at both targets suggests a relationship with the therapeutic effects of STN and GPi DBS, with both DBS targets being functionally connected with motor cortex at therapeutic stimulation frequencies.
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•Rats were stimulated intra-MRI at either the STN or GPi at 9 frequencies.•BOLD fMRI data were acquired during stimulation.•DBS at both targets produces positive BOLD in motor cortex peaking at 100Hz.•GPi DBS also produces contralateral negative BOLD peaking at 40Hz.•The frequency peak suggests a mechanistic relationship to clinical DBS.