Methodological considerations for behavioral studies relying on response time outcomes through online crowdsourcing platforms.

This perspective paper explores challenges associated with online crowdsourced data collection, particularly focusing on longitudinal tasks with time-sensitive outcomes like response latencies. Based on our research, we identify two significant sources of bias: technical shortcomings such as low, variable frame rates, and human factors, contributing to high attrition rates. We explored potential solutions to these problems, such as enforcing hardware acceleration and defining study-specific frame rate thresholds, as well as pre-screening participants and monitoring hardware performance and task engagement over each experimental session. With this discussion, we intend to provide recommendations on how to improve the quality and reliability of data collected via online crowdsourced platforms and emphasize the need for researchers to be cognizant of potential pitfalls in online research.

Dissociable Effects of Theta-Burst Repeated Transcranial Magnetic Stimulation to the Inferior Frontal Gyrus on Inhibitory Control in Nicotine Addiction.

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.

Impaired frontostriatal functional connectivity among chronic opioid using pain patients is associated with dysregulated affect.

Preclinical studies have shown effects of chronic exposure to addictive drugs on glutamatergic-mediated neuroplasticity in frontostriatal circuitry. These initial findings have been paralleled by human functional magnetic resonance imaging (fMRI) research demonstrating weaker frontostriatal resting-state functional connectivity (rsFC) among individuals with psychostimulant use disorders. However, there is a dearth of human imaging literature describing associations between long-term prescription opioid use, frontostriatal rsFC, and brain morphology among chronic pain patients. We hypothesized that prescription opioid users with chronic pain, as compared with healthy control subjects, would evidence weaker frontostriatal rsFC coupled with less frontostriatal gray matter volume (GMV). Further, those opioid use-related deficits in frontostriatal circuitry would be associated with negative affect and drug misuse. Prescription opioid users with chronic pain (n = 31) and drug-free healthy controls (n = 30) underwent a high-resolution anatomical and an eyes-closed resting-state functional scan. The opioid group, relative to controls, exhibited weaker frontostriatal rsFC, and less frontostriatal GMV in both L.NAc and L.vmPFC. Frontostriatal rsFC partially mediated group differences in negative affect. Within opioid users, L.NAc GMV predicted opioid misuse severity. The current study revealed that prescription opioid use in the context of chronic pain is associated with functional and structural abnormalities in frontostriatal circuitry. These results suggest that opioid use-related abnormalities in frontostriatal circuitry may undergird disturbances in affect that may contribute to the ongoing maintenance of opioid use and misuse. These findings warrant further examination of interventions to treat opioid pathophysiology in frontostriatal circuitry over the course of treatment.

Preliminary evidence for differential olfactory and trigeminal processing in combat veterans with and without PTSD.

Structural and functional changes in the olfactory system are increasingly implicated in the expression of PTSD. Still, very little is known about the neurobiological networks of trauma-related odor sensitivity or how they relate to other objective and subjective measures of olfaction and PTSD. The purpose of this study was to replicate prior findings and further characterize olfactory function in trauma-exposed combat veterans with and without PTSD. We also sought to extend this area of research by exploring the effects of time since the combat-related index trauma (TST) on post-trauma olfactory function, as well as by correlating odor-elicited brain activity to general olfactory ability and odor-elicited PTSD symptoms. Participants included combat veterans with PTSD (CV+PTSD; n = 21) or without any psychiatric disorder (CV-PTSD; n = 27). TST was coded as greater (n = 24) or less (n = 24) than 5 years. There were main effects and/or interaction for PTSD-status and TST across several parameters of olfactory function: odor detection, odor identification, ratings for trauma-related odor intensity and triggered PTSD symptoms, and trauma odor-elicited brain activation. Overall, results suggest olfactory impairment in chronic PTSD, but not necessarily in the earlier stages of the disorder, although some early-stage olfactory findings may be predictive of later olfactory impairment. Results also suggest that trauma-exposed individuals who never develop PTSD may demonstrate olfactory resiliency. Finally, results highlight a potentially unique role of trigeminal odor properties in the olfactory-PTSD relationship.

Association Between Baseline Corticothalamic-Mediated Inhibitory Control and Smoking Relapse Vulnerability.

Importance: Tobacco use disorder is associated with dysregulated neurocognitive function in the right inferior frontal gyrus (IFG)-one node in a corticothalamic inhibitory control (IC) network. Objective: To examine associations between IC neural circuitry structure and function and lapse/relapse vulnerability in 2 independent studies of adult smokers. Design, Setting, and Participants: In study 1, treatment-seeking smokers (n = 81) completed an IC task during functional magnetic resonance imaging (fMRI) before making a quit attempt and then were followed up for 10 weeks after their quit date. In study 2, a separate group of smokers (n = 26) performed the same IC task during fMRI, followed by completing a laboratory-based smoking relapse analog task. Study 1 was performed at Duke University Medical Center between 2008 and 2012; study 2 was conducted at the Medical University of South Carolina between 2013 and 2016. Main Outcomes and Measures: Associations between corticothalamic-mediated IC, gray-matter volume, and smoking lapse/relapse. Results: Of the 81 study participants in study 1 (cessation study), 45 were women (56%), with mean (SD) age, 38.4 (10.2) years. In study 1, smoking relapse was associated with less gray-matter volume (F1,74 = 28.32; familywise error P threshold = 0.03), greater IC task-related blood oxygenation level-dependent (BOLD) response in the right IFG (F1,78 = 14.87) and thalamus (F1,78 = 14.97) (P < .05), and weaker corticothalamic task-based functional connectivity (tbFC) (F1,77 = 5.87; P = .02). Of the 26 participants in study 2 (laboratory study), 15 were women (58%), with mean (SD) age, 34.9 (10.3). Similar to study 1, in study 2, greater IC-BOLD response in the right IFG (t23 = -2.49; ß = -0.47; P = .02), and weaker corticothalamic tbFC (t22 = 5.62; ß = 0.79; P < .001) were associated with smoking sooner during the smoking relapse-analog task. In both studies, corticothalamic tbFC mediated the association between IC performance and smoking outcomes. Conclusions and Relevance: In these 2 studies, baseline differences in corticothalamic circuitry function were associated with mediated IC and smoking relapse vulnerability. These findings warrant further examination of interventions for augmenting corticothalamic neurotransmission and enhancing IC during the course of tobacco use disorder treatment.

Burning odor-elicited anxiety in OEF/OIF combat veterans: Inverse relationship to gray matter volume in olfactory cortex.

Despite the anatomical overlap between the brain's fear/threat and olfactory systems, a very limited number of investigations have considered the role of odors and the central olfactory system in the pathophysiology of PTSD. The goal of the present study was to assess structural differences in primary and secondary olfactory cortex between combat veterans with and without PTSD (CV + PTSD, CV-PTSD, respectively). An additional goal was to determine the relationship between gray matter volume (GMV) in olfactory cortex and the distressing properties of burning-related odors. A region of interest voxel-based morphometric (VBM) approach was used to measure GMV in olfactory cortex in a well-characterized group of CV + PTSD (n = 20) and CV-PTSD (n = 25). Prior to the MRI exam, combat-related (i.e., burning rubber) and control odors were systematically sampled and rated according to their potential for eliciting PTSD symptoms. Results showed that CV + PTSD exhibited significantly reduced GMV in anterior piriform (primary olfactory) and orbitofrontal (secondary olfactory) cortices compared to CV-PTSD (both p < .01). For the entire group, GMV in bilateral anterior piriform cortex was inversely related to burning rubber odor-elicited memories of trauma (p < .05). GMV in orbitofrontal cortex was inversely related to both clinical and laboratory measures of PTSD symptoms (all p < .05). In addition to replicating an established inverse relationship between GMV in anxiety-associated brain structures and PTSD symptomatology, the present study extends those findings by being the first report of volumetric decreases in olfactory cortex that are inversely related to odor-elicited PTSD symptoms. Potential mechanisms underlying these findings are discussed.

Auditory driving of the autonomic nervous system: Listening to theta-frequency binaural beats post-exercise increases parasympathetic activation and sympathetic withdrawal.

Binaural beats are an auditory illusion perceived when two or more pure tones of similar frequencies are presented dichotically through stereo headphones. Although this phenomenon is thought to facilitate state changes (e.g., relaxation), few empirical studies have reported on whether binaural beats produce changes in autonomic arousal. Therefore, the present study investigated the effects of binaural beating on autonomic dynamics [heart rate variability (HRV)] during post-exercise relaxation. Subjects (n = 21; 18-29 years old) participated in a double-blind, placebo-controlled study during which binaural beats and placebo were administered over two randomized and counterbalanced sessions (within-subjects repeated-measures design). At the onset of each visit, subjects exercised for 20-min; post-exercise, subjects listened to either binaural beats ('wide-band' theta-frequency binaural beats) or placebo (carrier tones) for 20-min while relaxing alone in a quiet, low-light environment. Dependent variables consisted of high-frequency (HF, reflecting parasympathetic activity), low-frequency (LF, reflecting sympathetic and parasympathetic activity), and LF/HF normalized powers, as well as self-reported relaxation. As compared to the placebo visit, the binaural-beat visit resulted in greater self-reported relaxation, increased parasympathetic activation and increased sympathetic withdrawal. By the end of the 20-min relaxation period there were no observable differences in HRV between binaural-beat and placebo visits, although binaural-beat associated HRV significantly predicted subsequent reported relaxation. Findings suggest that listening to binaural beats may exert an acute influence on both LF and HF components of HRV and may increase subjective feelings of relaxation.