New Treatment Approaches For Addictive Brain Networks

Addiction is an increasing worldwide burden for the modern society.Neuroimaging studies from the last decades have revealed addiction as a brain disorder which involves dysregulations within not just reward circuitry but also inside prefrontal control and emotion processing pathways.Previous literatures have divided addiction cycle into three states during which addiction worsens and becomes chronic: binge/intoxication,withdrawal/negative affect and preoccupation/anticipation.Specifically,during binge/intoxication stage craving for drugs is related to the dysfunctional striatal areas after the neuroplasticity changes induced by intoxication.In contrast during withdrawal/negative affect,the amygdala dysregulation is accompanied by the emotional stressors after drug withdrawal.Although these neurobiological mechanisms of addiction have been systematically studied,the currently available treatment approaches for this disorder are far from satisfying in terms of abstinence rate,relapse rate and also the adverse effects after pharmacological treatments which urges the development of new and better treatments.During recent years,oxytocin and real-time fMRI neurofeedback(rtfMRI-NF)have been proposed to be two of the most promising neuromodulation and therapeutic approaches.Based on above background,we aimed to evaluate the modulative effects of oxytocin and rtfMRI-NF on the striatal and amygdalar networks in the healthy brain.Two studies were planned and carried out.In the first study with a randomized,double-blind,placebo-controlled design,we explored how oxytocin might modulate striatal networks in 141 healthy males.It was found that comparing with placebo treatment,oxytocin increased resting-state functional connectivity in the ventral caudate-dorsal anterior cingulate cortex pathway and the globus pallidus-motor cortex pathway,whereas it decreased connectivity between medial putamen and the posterior cerebellum area.These circuits were implicated to be involved in reward learning,craving and impulsive drug use.These neural effects supported the therapeutic potential of oxytocin for disorders including addiction by shifting the functional connectivity patterns of the striatal network.,which needs to be further validated by clinical studies in the future.In the second study,we used a within subject,sham-controlled design to investigate whether our training approach could enhance the prefrontal-amygdala connectivity and reduce anxiety.30 healthy males with high trait-anxiety were recruited as they share similar emotion regulation deficits with addictive populations.In this proof-of-concept study,we found that after experimental training but not sham training,the participants gained the ability to up-regulated the connectivity strength in the trained pathway.In the behavioral level,self-reported anxiety level was decrease by experimental training,which was associated with the connectivity increase as indicated by correlation analysis.These results validated our training approach in enhancing top-down emotion regulation and thus represented a potential new treatment approach for addictive populations by reducing the negative affect during drug withdrawal.With the above two studies,we explored the therapeutic potential of two novel treatments for addiction – oxytocin and rtfMRI-NF training on the striatal and amygdalar circuitries of the addictive brain network.Our results have validated these approaches by showing their effects on the positive and negative reinforcement neural mechanisms of addiction.Finally,in this thesis as we only focused on healthy participants,the above results shall be further validated in clinical populations by future studies.