Thalamic volume and functional connectivity are associated with nicotine dependence severity and craving.

Tobacco smoking is associated with deleterious health outcomes. Most smokers want to quit smoking, yet relapse rates are high. Understanding neural differences associated with tobacco use may help generate novel treatment options. Several animal studies have recently highlighted the central role of the thalamus in substance use disorders, but this research focus has been understudied in human smokers. Here, we investigated associations between structural and functional magnetic resonance imaging measures of the thalamus and its subnuclei to distinct smoking characteristics. We acquired anatomical scans of 32 smokers as well as functional resting-state scans before and after a cue-reactivity task. Thalamic functional connectivity was associated with craving and dependence severity, whereas the volume of the thalamus was associated with dependence severity only. Craving, which fluctuates rapidly, was best characterized by differences in brain function, whereas the rather persistent syndrome of dependence severity was associated with both brain structural differences and function. Our study supports the notion that functional versus structural measures tend to be associated with behavioural measures that evolve at faster versus slower temporal scales, respectively. It confirms the importance of the thalamus to understand mechanisms of addiction and highlights it as a potential target for brain-based interventions to support smoking cessation, such as brain stimulation and neurofeedback.

Predictors of real-time fMRI neurofeedback performance and improvement - A machine learning mega-analysis.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing.

Pre- and post-task resting-state differs in clinical populations.

Resting-state functional connectivity has generated great hopes as a potential brain biomarker for improving prevention, diagnosis, and treatment in psychiatry. This neuroimaging protocol can routinely be performed by patients and does not depend on the specificities of a task. Thus, it seems ideal for big data approaches that require aggregating data across multiple studies and sites. However, technical variability, diverging data analysis approaches, and differences in data acquisition protocols introduce heterogeneity to the aggregated data. Besides these technical aspects, a prior task that changes the psychological state of participants might also contribute to heterogeneity. In healthy participants, studies have shown that behavioral tasks can influence resting-state measures, but such effects have not yet been reported in clinical populations. Here, we fill this knowledge gap by comparing resting-state functional connectivity before and after clinically relevant tasks in two clinical conditions, namely substance use disorders and phobias. The tasks consisted of viewing craving-inducing and spider anxiety provoking pictures that are frequently used in cue-reactivity studies and exposure therapy. We found distinct pre- vs post-task resting-state connectivity differences in each group, as well as decreased thalamo-cortical and increased intra-thalamic connectivity which might be associated with decreased vigilance in both groups. Our results confirm that resting-state measures can be strongly influenced by prior emotion-inducing tasks that need to be taken into account when pooling resting-state scans for clinical biomarker detection. This demands that resting-state datasets should include a complete description of the experimental design, especially when a task preceded data collection.