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Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

ABSTRACT: Introduction:Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options for these symptoms, recent studies with transcranial magnetic stimulation (TMS), applying intermittent theta-burst stimulation (iTBS) to dorsolateral prefrontal cortex (DLPFC), suggest beneficial effects for certain aspects of cognition, such as memory or inhibitory control. While TMS is non-invasive, its results are transient and require repeated application. Subcortical DBS targets have strong reciprocal connections with prefrontal cortex, such that iTBS through the permanently implanted lead might represent a more durable solution. Here we demonstrate safety and feasibility for delivering iTBS from the DBS electrode and explore changes in DLPFC electrophysiology. Methods:We enrolled seven participants with medically refractory Parkinson's disease who underwent DBS surgery targeting either the subthalamic nucleus (STN) or globus pallidus interna (GPi). We temporarily placed an electrocorticography strip over DLPFC through the DBS burr hole. After placement of the DBS electrode into either GPi (n = 3) or STN (n = 4), awake subjects rested quietly during iTBS (three 50-Hz pulses delivered at 5 Hz for 2 s, followed by 8 s of rest). We contrasted power spectra in DLPFC local field potentials during iTBS versus at rest, as well as between iTBS and conventional high-frequency stimulation (HFS). Results:Dominant frequencies in DLPFC at rest varied among subjects and along the subdural strip electrode, though they were generally localized in theta (3-8 Hz) and/or beta (10-30 Hz) ranges. Both iTBS and HFS were well-tolerated and imperceptible. iTBS increased theta-frequency activity more than HFS. Further, GPi stimulation resulted in significantly greater theta-power versus STN stimulation in our sample. Conclusion:Acute subcortical iTBS from the DBS electrode was safe and well-tolerated. This novel stimulation pattern delivered from the GPi may increase theta-frequency power in ipsilateral DLPFC. Future studies will confirm these changes in DLPFC activity during iTBS and evaluate whether they are associated with improvements in cognitive or behavioral symptoms from PD.

SUBMITTER: Bentley JN

PROVIDER: S-EPMC7006239 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

Bentley J Nicole JN Irwin Zachary T ZT Black Sarah D SD Roach Megan L ML Vaden Ryan J RJ Gonzalez Christopher L CL Khan Anas U AU El-Sayed Galal A GA Knight Robert T RT Guthrie Barton L BL Walker Harrison C HC

Frontiers in neuroscience 20200131

<h4>Introduction</h4>Cognitive symptoms from Parkinson's disease cause severe disability and significantly limit quality of life. Little is known about mechanisms of cognitive impairment in PD, although aberrant oscillatory activity in basal ganglia-thalamo-prefrontal cortical circuits likely plays an important role. While continuous high-frequency deep brain stimulation (DBS) improves motor symptoms, it is generally ineffective for cognitive symptoms. Although we lack robust treatment options f ...[more]

PMID: 32082113

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Project description:BackgroundPolydrug abuse is common among opioid users. Individuals who use both heroin and methamphetamine (MA) have been shown to experience a wide range of cognitive deficits. Previous research shows that repetitive transcranial magnetic stimulation (rTMS) can change cerebral cortical excitability and regulate neurotransmitter concentration, which could improve cognitive function in drug addiction. However, the stimulation time, location, and possible mechanisms of rTMS are uncertain.Methods56 patients with polydrug use disorder were randomized to receive 20 sessions of 10 Hz rTMS (n = 19), iTBS (n = 19), or sham iTBS (n = 18) to the left DLPFC. All patients used MA and heroin concurrently. Cognitive function was assessed and several related proteins including EPI, GABA-Aα5, IL-10, etc. were quantified by ELISA before and after the treatment.ResultsBaseline RBANS scores were lower than normal for age (77.25; IQR 71.5-85.5). After 20 treatment sessions, in the iTBS group, the RBANS score increased by 11.95 (95% CI 0.02-13.90, p = 0.05). In particular, there were improvements in memory and attention as well as social cognition. Following treatment, serum EPI and GABA-Aα5 were reduced and IL-10 was elevated. The improvement of immediate memory was negatively correlated with GABA-Aα5 (r = -0.646, p = 0.017), and attention was positively correlated with IL-10 (r = 0.610, p = 0.027). In the 10 Hz rTMS group, the improvement of the RBANS total score (80.21 ± 14.08 before vs.84.32 ± 13.80 after) and immediate memory (74.53 ± 16.65 before vs.77.53 ± 17.78 after) was statistically significant compared with the baseline (p < 0.05). However, compared with the iTBS group, the improvement was small and the difference was statistically significant. There was no statistically significant change in the sham group (78.00 ± 12.91 before vs.79.89 ± 10.92 after; p > 0.05).ConclusionIntermittent theta burst stimulation to the left DLPFC may improve cognitive function in polydrug use disorder patients. Its efficacy appears to be better than that of 10 Hz rTMS. The improvement of cognitive function may be related to GABA-Aα5 and IL-10. Our findings preliminarily demonstrate the clinical value of iTBS to the DLPFC to augment neurocognitive recovery in polydrug use disorders.

Dataset Information

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

Publications

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC).

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