Mesocorticolimbic system reactivity to alcohol use-related visual cues as a function of alcohol sensitivity phenotype: A pilot fMRI study.

Low sensitivity (LS) to alcohol is a risk factor for alcohol use disorder (AUD). Compared to peers with high sensitivity (HS), LS individuals drink more, report more problems, and exhibit potentiated alcohol cue reactivity (ACR). Heightened ACR suggests LS confers AUD risk via incentive sensitization, which is thought to take place in the mesocorticolimbic system. This study examined neural ACR in LS and HS individuals. Young adults (N = 32, M age=20.3) were recruited based on the Alcohol Sensitivity Questionnaire (HS: n = 16; LS: n = 16; 9 females/group). Participants completed an event-related fMRI ACR task. Group LS had higher ACR in left ventrolateral prefrontal cortex than group HS. In group LS, ACR in left caudomedial orbitofrontal cortex or left putamen was low at low alcohol use levels and high at heavier or more problematic alcohol use levels, whereas the opposite was true in group HS. Alcohol use level also was associated with the level of ACR in left substantia nigra among males in group LS. Taken together, results suggest elevated mesocorticolimbic ACR among LS individuals, especially those using alcohol at hazardous levels. Future studies with larger samples are warranted to determine the neurobiological loci underlying LS-based amplified ACR and AUD risk.

Effects of Hyperdirect Pathway Theta Burst Transcranial Magnetic Stimulation on Inhibitory Control, Craving, and Smoking in Adults With Nicotine Dependence: A Double-Blind, Randomized Crossover Trial.

BACKGROUND: Nicotine dependence is associated with dysregulated hyperdirect pathway (HDP)-mediated inhibitory control (IC). However, there are currently no evidence-based treatments that have been shown to target the HDP to improve IC and reduce cigarette cravings and smoking. METHODS: Following a baseline nonstimulation control session, this study (N = 37; female: n = 17) used a double-blind, randomized crossover design to examine the behavioral and neural effects of intermittent theta burst stimulation (iTBS) and continuous TBS (cTBS) to the right inferior frontal gyrus (rIFG)-a key cortical node of the HDP. Associations between treatment effects were also explored. RESULTS: At baseline, HDP IC task-state functional connectivity was positively associated with IC task performance, which confirmed the association between HDP circuit function and IC. Compared with iTBS, rIFG cTBS improved IC task performance. Compared with the baseline nonstimulation control session, both TBS conditions reduced cigarette craving and smoking; however, although craving and smoking were lower for cTBS, no differences were found between the two active conditions. In addition, although HDP IC task-state functional connectivity was greater following cTBS than iTBS, there was no significant difference between conditions. Finally, cTBS-induced improvement in IC task performance was associated with reduced craving, and cTBS-induced reduction in craving was associated with reduced smoking. CONCLUSIONS: These findings warrant further investigation into the effects of rIFG cTBS for increasing IC and reducing craving and smoking among individuals with nicotine dependence. Future sham-controlled cTBS studies may help further elucidate the mechanisms by which rIFG cTBS mediates IC and smoking behavior.

Right inferior frontal gyrus theta-burst stimulation reduces smoking behaviors and strengthens fronto-striatal-limbic resting-state functional connectivity: a randomized crossover trial.

Introduction: Functional and anatomical irregularities in the right inferior frontal gyrus (rIFG), a ventrolateral prefrontal region that mediates top-down inhibitory control over prepotent behavioral responding, are implicated in the ongoing maintenance of nicotine dependence (ND). However, there is little research on the effects of neuromodulation of the rIFG on smoking behavior, inhibitory control, and resting-state functional connectivity (rsFC) among individuals with ND. Methods: In this double-blind, crossover, theta-burst stimulation (TBS) study, adults with ND (N = 31; female: n = 15) completed a baseline session and were then randomized to two counterbalanced sessions of functionally neuronavigated TBS to the rIFG: continuous TBS (cTBS) on 1 day and intermittent TBS (iTBS) on another. Differences in cigarette cravings, smoking, and fronto-striatal-limbic rsFC were assessed. Results: Relative to baseline, cTBS significantly reduced appetitive and withdrawal cravings immediately after treatment. The effects of cTBS on withdrawal craving persisted for 24 h, as well as produced a reduction in smoking. Furthermore, cTBS significantly strengthened rsFC between the rIFG pars opercularis and subcallosal cingulate (fronto-striatal circuit), and between the rIFG pars opercularis and the right posterior parahippocampal gyrus (fronto-limbic circuit). At post-24 h, cTBS-induced increase in fronto-striatal rsFC was significantly associated with less appetitive craving, while the increase in fronto-limbic rsFC was significantly associated with less withdrawal craving and smoking. Discussion: These findings warrant further investigation into the potential value of rIFG cTBS to attenuate smoking behavior among individuals with ND.

Associations Between the Wisconsin Inventory of Smoking Dependence Motives and Regional Brain Volumes in Adult Smokers.

INTRODUCTION: The Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) is a 68-item questionnaire to assess nicotine dependence as a multifactorial construct based on 13 theoretically derived smoking motives. Chronic smoking is associated with structural changes in brain regions implicated in the maintenance of smoking behavior; however, associations between brain morphometry and the various reinforcing components of smoking behavior remain unexamined. The present study investigated the potential association between smoking dependence motives and regional brain volumes in a cohort of 254 adult smokers. AIMS AND METHODS: The WISDM-68 was administered to participants at the baseline session. Structural magnetic resonance brain imaging (MRI) data from 254 adult smokers (Mage = 42.7 ± 11.4) with moderate to severe nicotine dependence (MFTND = 5.4 ± 2.0) smoking for at least 2 years (Myears = 24.3 ± 11.8) were collected and analyzed with Freesurfer. RESULTS: Vertex-wise cluster analysis revealed that high scores on the WISDM-68 composite, secondary dependence motives (SDM) composite, and multiple SDM subscales were associated with lower cortical volume in the right lateral prefrontal cortex (cluster-wise p's < .035). Analysis of subcortical volumes (ie, nucleus accumbens, amygdala, caudate, and pallidum) revealed several significant associations with WISDM-68 subscales, dependence severity (Fagerström Test for Nicotine Dependence), and overall exposure (pack-years). No significant associations between cortical volume and other nicotine dependence measures or pack-years were observed. CONCLUSIONS: Results suggest that smoking motives may play a larger role in cortical abnormalities than addiction severity and smoking exposure per se, whereas subcortical volumes are associated with smoking motives, addiction severity, and smoking exposure. IMPLICATIONS: The present study reports novel associations between the various reinforcing components of smoking behavior assessed by the WISDM-68 and regional brain volumes. Results suggest that the underlying emotional, cognitive, and sensory processes that drive non-compulsive smoking behaviors may play a larger role in gray matter abnormalities of smokers than smoking exposure or addiction severity.

Associations between right inferior frontal gyrus morphometry and inhibitory control in individuals with nicotine dependence.

BACKGROUND: The hyperdirect pathway - a circuit involved in executing inhibitory control (IC) - is dysregulated among individuals with nicotine dependence. The right inferior frontal gyrus (rIFG), a cortical input to the hyperdirect circuit, has been shown to be functionally and structurally altered among nicotine-dependent people who smoke. The rIFG is composed of 3 cytoarchitecturally distinct subregions: The pars opercularis, pars triangularis, and pars orbitalis. The present study assessed the relationship between rIFG subregion morphometry and inhibitory control among individuals with nicotine dependence. METHODS: Behavioral and magnetic resonance brain imaging (MRI) data from 127 nicotine-dependent adults who smoke (MFTND = 5.4, ± 1.9; MCPD = 18.3, ± 7.0; Myears = 25.04, ± 11.97) (Mage = 42.9, ± 11.1) were assessed. Brain morphometry was assessed from T1-weighted MRIs using Freesurfer. IC was assessed with a response-inhibition Go/Go/No-Go (GGNG) task and a smoking relapse analog task (SRT). RESULTS AND CONCLUSIONS: Vertex-wise analyses revealed that GGNG task scores were positively associated with cortical thickness and volume in the right pars triangularis (cluster-wise p = 0.006, 90% CI = 0.003 - 0.009; cluster-wise p = 0.040, 90% CI = 0.032 - 0.048), and the ability to inhibit ad lib smoking during the SRT was positively associated with cortical thickness in the right pars orbitalis (cluster-wise p = 0.011, 90% CI = 0.007 - 0.015). Our results indicate that cortical thickness of distinct rIFG subregions may serve as biomarkers for unique forms of IC deficits.

The relationship between metabolic control and basal ganglia morphometry and function in individuals with early-treated phenylketonuria.

Abnormalities of the cortical white matter are the most prominent and widely-reported neurological findings in individuals with early-treated phenylketonuria (ETPKU). Much less is known regarding the effects of ETPKU on gray matter structures in the brain such as the basal ganglia. Previous findings on basal ganglia in ETPKU have been mixed. The current study was designed to further elucidate the effects of ETPKU and elevated phe levels on the morphometry of basal ganglia structures (i.e., putamen, caudate nucleus, nucleus accumbens, and globus pallidus). High resolution magnetic resonance imaging (MRI) data was collected from a sample of 37 adults with ETPKU and a demographically-matched comparison group of 33 individuals without PKU. No overall group differences (ETPKU vs. non-PKU) in basal ganglia volumes were observed. However, within the ETPKU group, poorer metabolic control (as reflected by higher blood phenylalanine levels) was associated with larger putamen volume. Vertex-wise shape analysis revealed that the volume increase was accompanied by shape changes in the middle left putamen. Consistent with this area's role in motor control, a significant correlation between left putamen volume and motor performance was also observed. Additional research is needed to fully understand the cellular level processes underlying this effect as well as to better understand the clinical impact of these morphometric changes and their potential relation to treatment response.

Pilot Study of Real-World Monitoring of the Heart Rate Variability in Amyotrophic Lateral Sclerosis.

Aims: Cardiovascular dysautonomia may impact the quality of life and survival in amyotrophic lateral sclerosis (ALS). Such dysfunction is not systematically assessed in these patients. Wearable devices could help. The feasibility of a wearable biosensor to detect heart rate variability (HRV), a physiological marker of sympathovagal balance, was studied for the first time in real-world settings in ALS. Methods: Five ALS patients (two early/three late; one bulbar-onset; mildly-to-moderately disabled) and five age/sex/BMI/comorbidities-matched controls underwent assessment of 3-day HRV via VitalConnect biosensor (worn on the left thorax). De-identified data captured by the biosensor were transferred to a secure cloud server via a relay Bluetooth device. Baseline ALS severity/anxiety and physical activity during testing were documented/quantified. Time-domain HRV measures (i.e., pNN50) were analyzed. Results: An overall 3-day abnormal HRV (pNN50 < 3%), was found in three out of five patients (mean ± SD for the group, 2.49 ± 1.51). Similar changes were reported in controls (12.32 ± 21.14%). There were no statistically significant relationships between pNN50 values and baseline anxiety or physical activity during the tested days (p > 0.05 for both groups). A negative correlation was found between pNN50 values and age in patients (p = 0.01) and controls (p = 0.09), which is similar with what is found in the general population. In line with prior studies, pNN50 values were independent of disease stage (p = 0.6) and disability (p = 0.4). Conclusions: These preliminary results suggest that remote HRV measures using the VitalConnect is feasible and may constitute an improved strategy to provide insights into sympathovagal balance in ALS. Further work with larger sample sizes is warranted.

Archerfish respond to a hunting robotic conspecific.

While the unique hunting behavior of archerfish has received considerable scientific attention, the specific social cues that govern behaviors like intraspecific kleptoparasitism in the species are less understood. This paper asks whether the use of a robotic facsimile representing an archerfish can elicit a social response if it approximates an archerfish's appearance, along with key features of its hunting behavior. We found that the fish respond to the robot when it hunted, as indicated by decreasing distances between the robot and fish (and among the fish) during the robot's hunting behavior sequence, as well as higher net transfer entropy when the robot was hunting. These effects were present even when the robot's "hunt" was unproductive and did not result in food. The temporal pattern of fish approach to the robot and each other indicated that the segment of robot hunting behavior proximal to the robotic facsimile shot elicited fish behavior initially. However, earlier cues in the robot's hunting sequence became important following more experience with a food contingency. This indicates that further studies could use a robotic facsimile to conduct a detailed stimulus analysis, changing aspects of the robot's appearance and behavior to uncover the basic mechanisms of information transfer among individuals in a social hunting scenario.

Target capture strategy selection in a simulated marksmanship task.

This paper examines how individuals track targets that move in relatively unpredictable trajectories. Gaze and behavioural data were captured as twenty two participants learned a simulated competitive marksmanship task known colloquially as the Death Star over six training days. Participants spontaneously selected one of two consistent target-tracking strategies with approximately equal probability. Participants employed either chasing behaviour, in which gaze follows a target's trajectory before a shot, or ambushing behaviour, wherein gaze anticipates the trajectory and the participant intercepts a moving target predictively. All participants improved in task performance measures (completion time and number of shots), but did so at the expense of accuracy in missed shot attempts. Surprisingly, neither behavioural strategy offered a significant advantage in task performance measures, indicating that either may be equally effective in tackling a hand-eye coordination task with complex target motion such as the Death Star.

A method for measuring manual position control.

There is no generally accepted method for measuring manual position control. We developed a method for doing so. We asked university students to hold a handle that had one rotational degree of freedom. The angular position of the handle depended on the degree of pronation-supination of the forearm. The subjects' task was to hold the handle as steadily as possible to keep a needle positioned in a pie-shaped target zone on a computer screen. If the needle remained in the zone for 0.5s, the gain of the feedback loop increased; otherwise the gain decreased or remained at the starting value of 1. Through this adaptive procedure, we estimated the maximum gain that could be achieved at each of the four pronation-supination angles we tested (thumb up, thumb down, thumb in, and thumb out) for each hand. Consistent with previous research on manual control, and so validating our measure, we found that our participants, all of whom were right-handed, were better able to maintain the needle in the target zone when they used the right hand than when they used the left hand and when they used midrange wrist postures (thumb up or in) rather than extreme wrist postures (thumb down or out). The method provides a valid test of manual position control and holds promise for addressing basic-research and practical questions.

The promise of cyborg intelligence.

Yu et al. (2016) demonstrated that algorithms designed to find efficient routes in standard mazes can be integrated with the natural processes controlling rat navigation and spatial choices, and they pointed out the promise of such "cyborg intelligence" for biorobotic applications. Here, we briefly describe Yu et al.'s work, explore its relevance to the study of comparative cognition, and indicate how work involving cyborg intelligence would benefit from interdisciplinary collaboration between behavioral scientists and engineers.