Dataset Information

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study.

ABSTRACT:

Background

Alcohol use disorder (AUD) is associated with elevated brain response to cues. Recent studies have suggested that theta burst stimulation (TBS) to the medial prefrontal cortex (MPFC) can decrease reactivity to cues in a transdiagnostic manner. The goal of this clinical trial was to evaluate the effect of continuous TBS as a tool to decrease drinking behavior and brain reactivity to alcohol cues among individuals with AUD.

Methods

A total of 50 individuals with AUD were recruited from an intensive outpatient treatment program. Using a randomized, double-blind, sham-controlled design, participants received 10 sessions of continuous TBS (left frontal pole, 1 session/10 days, 110% resting motor threshold, 3600 pulse/session, cue provocation before and during session). Brain reactivity to alcohol cues was acquired at four time points: at baseline and after all TBS sessions (1 month, 2 months, and 3 months).

Results

Overall, 80% of the participants completed all TBS sessions. Individuals who received real TBS were 2.71 times more likely to remain enrolled in the study after 3 months and 3.09 times more likely to remain sober 3 months after treatment initiation. Real TBS also led to a significantly greater reduction in brain reactivity to alcohol cues, specifically a reduction in MPFC-striatum and MPFC-insula connectivity 2 and 3 months after TBS treatment.

Conclusions

Ten days of MPFC TBS is well tolerated, reduces drinking, and decreases brain reactivity to alcohol cues for up to 3 months after treatment initiation. These results pave a critical next step in the path toward developing transcranial magnetic stimulation as an intervention for AUD and disorders associated with elevated cue reactivity.

SUBMITTER: McCalley DM

PROVIDER: S-EPMC10140456 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study.

McCalley Daniel M DM Kaur Navneet N Wolf Julia P JP Contreras Ingrid E IE Book Sarah W SW Smith Joshua P JP Hanlon Colleen A CA

Biological psychiatry global open science 20220315 2

<h4>Background</h4>Alcohol use disorder (AUD) is associated with elevated brain response to cues. Recent studies have suggested that theta burst stimulation (TBS) to the medial prefrontal cortex (MPFC) can decrease reactivity to cues in a transdiagnostic manner. The goal of this clinical trial was to evaluate the effect of continuous TBS as a tool to decrease drinking behavior and brain reactivity to alcohol cues among individuals with AUD.<h4>Methods</h4>A total of 50 individuals with AUD were ...[more]

PMID: 37124360

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Project description:IntroductionCognitive 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.MethodsWe 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).ResultsDominant 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.ConclusionAcute 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.

Project description:The dorsomedial prefrontal cortex (DMPFC) plays a pivotal role in depression and anxiosomatic symptom modulation. However, DMPFC stimulation using a double-cone coil has demonstrated inconsistent results for antidepressant efficacy. No study thus far has investigated the antidepressant and anti-anxiosomatic effects of prolonged intermittent theta-burst stimulation (piTBS) bilaterally over DMPFC. Furthermore, head-to-head comparisons of antidepressant effects between standard iTBS and piTBS warrant investigation. This double-blind, randomized, sham-controlled trial recruited 34 patients with highly treatment-resistant depression (TRD) unresponsive to antidepressants and standard repetitive transcranial magnetic stimulation (rTMS)/piTBS. These patients were randomly assigned to one of three monotherapy groups (standard iTBS, piTBS, or sham), with treatment administered bilaterally over the DMPFC twice per day for 3 weeks. The primary outcome was the overall changes of 17-item Hamilton Depression Rating Scale (HDRS-17) over 3-weeks intervention. The changes in Depression and Somatic Symptoms Scale (DSSS) as the secondary outcome and the anxiosomatic cluster symptoms as rated by HDRS-17 as the post-hoc outcome were measured. Multivariable generalized estimating equation analysis was performed. Although no differences in overall HDRS-17 changes between three groups were found, the antidepressant efficacy based on DSSS was higher in piTBS than in iTBS and sham at week 3 (group effect,p = 0.003, post-hoc: piTBS > iTBS, p = 0.002; piTBS > sham, p = 0.038). In post-hoc analyses, piTBS had more alleviation in anxiosomatic symptoms than iTBS (group effect, p = 0.002; post-hoc, p = 0.001). This first randomized sham-controlled study directly compared piTBS and iTBS targeting the DMPFC using a figure-of-8 coil and found piTBS may fail to demonstrate a significant antidepressant effect on overall depressive symptoms, but piTBS seems superior in alleviating anxiosomatic symptoms, even in depressed patients with high treatment resistance. This Trial registration (Registration number: NCT04037592). URL: https://clinicaltrials.gov/ct2/show/NCT04037592 .

Dataset Information

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study.

Background

Methods

Results

Conclusions

Publications

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study.

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