Abstract
Nicotine addiction, like other substance use disorders (SUD’s), is associated with deficits in prefrontal mediated inhibitory control. The strength of inhibitory control task-based functional connectivity (tbFC) between the right inferior frontal gyrus (r.IFG) and thalamus (corticothalamic circuit) mediates the association between successful inhibition and smoking relapse vulnerability. However, the potential efficacy of theta burst stimulation (TBS) to the r.IFG, a treatment known to alter clinical symptoms among neuropsychiatric patients, has not been reported in a SUD population. This study utilized fMRI guided neuronavigation to examine the effects of TBS on inhibitory control among nicotine dependent individuals. Participants (N=12) were scanned while performing an inhibitory control task known to elicit inhibition-related activity in the r.IFG. Using a randomized, counterbalanced cross-over design, participants then received TBS over two visits: excitatory (iTBS) on one visit and inhibitory (cTBS) TBS on the other visit. The effects of each TBS condition on subsequent inhibitory control task performance were examined. A significant condition x time interaction was identified on trials requiring inhibitory control (F (1,10) = 7.27, p = .022, D = 1.63). iTBS improved inhibitory control, whereas cTBS impaired inhibitory control. Brain stimulation did not influence performance in control conditions including novelty detection and response execution. This is the first study to demonstrate that non-invasive neural stimulation using iTBS to the r.IFG enhances baseline inhibitory control among individuals with a SUD. Further research is needed to directly examine the potential parametric effects of TBS on corticothalamic tbFC in individuals with a SUD.
Highlights
Substance use disorders (SUDs) are characterized by significant disruptions to multiple forms of executive function [1] and the extant literature implicates dysregulated inhibitory control, one specific form of executive function, as a transdiagnostic indicator of relapse vulnerability across substances of abuse [2]
There is overwhelming evidence that the r.IFG is a critical cortical node in the network responsible for initiating “stop” signals related to a prepotent motor response [33], and yet there is a dearth of studies reporting on the effects of TMS in general on r.IFG and, to the best our knowledge, these findings are the first to demonstrate that non-invasive neural stimulation using Intermittent Theta Burst Stimulation (iTBS) to the r.IFG enhances baseline inhibitory control among individuals with a substance use disorder
We acknowledge that theta burst stimulation (TBS) to the pre-SMA—a cortical node in the corticothalamic pathway—has been shown to impact inhibitory control task performance among healthy control participants [26, 42, 43] and warrants examination in future studies
Summary
Substance use disorders (SUDs) are characterized by significant disruptions to multiple forms of executive function [1] and the extant literature implicates dysregulated inhibitory control, one specific form of executive function, as a transdiagnostic indicator of relapse vulnerability across substances of abuse [2]. In the context of tobacco use disorder (nicotine addiction), smokers, as compared to non-smokers, exhibit significantly worse performance on tasks that probe inhibitory control (IC) [3,4,5]; and among smokers, smoking abstinence as compared to satiety, further disrupts inhibitory control task performance [6, 7]. Individuals with a substance use disorder [2], including tobacco use disorder [15,16,17], exhibit greater fMRI BOLD response in the r.IFG during task probes of attention [18] and inhibitory control [6] that may represent a compensatory mechanism to meet task demands. Given strong evidence for the involvement of r.IFG in inhibitory control and smoking related dysregulation in r.IFG mediated inhibition, examining whether neural stimulation to the r.IFG can modulate inhibitory control in smokers represents an important avenue for examination
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