Amir Hossein Dakhili

Background and purpose: Olfactory stimuli are known to have a significant effect on cognitive functions. However, their effect on risky decision-making remains unclear. The present study aimed to investigate this effect, using functional magnetic resonance imaging (fMRI) and a novel mixed gambling task. Materials and Methods: Twenty-nine healthy participants with normal olfactory function underwent fMRI scanning while performing a gambling task under exposure to pleasant and unpleasant odors, as well as fresh air and a neutral condition without any olfactory stimulation. ROI-to-ROI functional connectivity analyses were conducted, focusing on regions involved in olfactory processing and risky decision-making, including dorsolateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), insula, anterior cingulate cortex (ACC), piriform cortex, and uncus. Results: Pleasant odors, compared to the neutral condition, enhanced connectivity between OFC and vmPFC. Fresh air, compared to neutral, reduced connectivity between the DLPFC, OFC, vmPFC, piriform and insula, while increasing connectivity between the piriform and uncus. Unpleasant odors, compared to neutral, increased connectivity between the vmPFC, OFC, and ACC. Unpleasant odors, compared to fresh air, enhanced connectivity between the DLPFC and insula but reduced connectivity between the insula and OFC. Pleasant odors, compared to unpleasant odors, increased connectivity between the insula and OFC (p-FDR < 0.05). Conclusion: Olfactory stimuli modulate neural networks underlying risky decision-making during a mixed gambling task. These findings highlight the clinical relevance of olfactory modulation for addiction research and the potential of functional connectivity analyses to provide a foundation for personalised interventions aimed at reducing maladaptive risk-taking behavior and cue-driven vulnerability.

Background: Drug-related cue-reactivity, dysfunctional negative emotion processing, and response-disinhibition constitute three core aspects of methamphetamine use disorder (MUD). These phenomena have been studied independently, but the neuroscientific literature on their interaction in addictive disorders remains scant. Methods: 62 individuals with MUD were scanned when responding to the geometric Go or No-Go cues superimposed over blank, neutral, negative-emotional and drug-related background images. Neural correlates of drug and negative-emotional cue-reactivity, response-inhibition and their interactions were estimated, and methamphetamine cue-reactivity was compared between individuals with MUD and 23 healthy controls. Relationships between behavioral characteristics and observed activations were investigated. Results: Individuals with MUD had longer reaction times and more errors in drug and negative-emotional compared to blank blocks, and more omission errors in drug compared to neutral blocks. They showed higher drug cue-reactivity than controls across prefrontal, fusiform, and visual regions (Z > 3.1, p-corrected<0.05). Response-inhibition was associated with precuneal, inferior parietal, anterior cingulate, temporal, and inferior frontal activations (Z > 3.1, p-corrected<0.05). Response-inhibition in drug cue blocks coincided with higher activations in the visual cortex and lower activations in the paracentral lobule and superior and inferior frontal gyri, while inhibition during negative-emotional blocks led to higher superior parietal, fusiform, and lateral occipital activations (Z > 3.1, p-corrected<0.05). Conclusion: Drug cue-reactivity may impair response inhibition partly through activating dis-inhibitory regions, while temporal and parietal activations associated with response-inhibition in negative blocks suggest compensatory activity. Results suggest that drug and negative-emotional cue-reactivity influence response-inhibition, and the study of these interactions may aid mechanistic understanding of methamphetamine use disorder.

Introduction: Cannabis use disorder (CUD) affects ∼33 million people globally and can be underscored by intense cravings to use cannabis, which can trigger compulsive use and relapse. Functional MRI (fMRI) evidence demonstrates hyperactivity of addiction brain pathways during cannabis cue- reactivity, consistent with prominent neuroscientific theories of addiction, particularly within the anterior cingulate cortex (ACC). The ACC also emerges as a key region of real- time fMRI- based neurofeedback (fMRI- neurofeedback) studies demonstrating voluntary changes during cravings in persons who use substances. However, this notion is untested in CUD. Methods and analysis: We aim to develop a protocol that tests the feasibility of fMRI- neurofeedback to enable persons with a moderate- to- severe CUD to increase the activity of the ACC during cannabis- induced craving to provide mechanistic insights on treatment targets; and decrease ACC activity during cue- induced craving to pave the way for reducing brain reactivity. The primary outcome measure is the change in ACC activity during fMRI- neurofeedback compared with a non- regulation condition. Ethics and dissemination: This feasibility study has been approved by the Human Research Ethics Committee of Australian Catholic University. On completion, the findings from this study will be published in academic journals, presented at conferences and disseminated to clinicians and to individuals who use cannabis. The results from this feasibility study have the potential to inform the conduct of powered trials to examine how fMRI- neurofeedback can identify and reduce craving- related brain dysfunction in CUD.