Shared and Unique Neural Circuitry Underlying Temporally Unpredictable Threat and Reward Processing

Temporally unpredictable stimuli influence behavior across species, as previously demonstrated for sequences of simple threats and rewards with fixed or variable onset. Neuroimaging studies have identified a specific frontolimbic circuit that may become engaged during the anticipation of temporally unpredictable threat (U-threat). However, the neural mechanisms underlying processing of temporally unpredictable reward (U-reward) are incompletely understood. It is also unclear whether these processes are mediated by overlapping or distinct neural systems. These knowledge gaps are noteworthy given that disruptions within these neural systems may lead to maladaptive responding to uncertainty. Here, using functional magnetic resonance imaging (fMRI) data from a sample of 159 young adults, we showed that anticipation of both U-threat and U-reward elicited activation in the right anterior insula, right ventral anterior nucleus of the thalamus and right inferior frontal gyrus. U-threat also activated the right posterior insula and dorsal anterior cingulate cortex, relative to U-reward. In contrast, U-reward elicited activation in the right fusiform and left middle occipital gyrus, relative to U- threat. Although there is some overlap in the neural circuitry underlying anticipation of U-threat and U-reward, these processes appear to be largely mediated by distinct circuits. Future studies are needed to corroborate and extend these preliminary findings

Effective Connectivity During Threat Processing in Internalizing Psychopathology and Alcohol Use Disorder

Heightened reactivity to uncertain threats (U-threats) has emerged as a transdiagnostic marker of internalizing psychopathologies (IPs) as evidenced by increased startle responses. A developing theory and recent research also suggest that heightened reactivity to U-threats may be an important individual difference factor that facilitates excessive drinking as a means of avoidance-based coping and characterizes individuals with current and past alcohol use disorder (AUD). Previous studies have used fMRI to identify the neural correlates of heightened responses to U-threat and consistently observed increased activation in the anterior insula (AIC), anteromedial (AM) thalamus and dorsal anterior cingulate cortex (dACC); however, no study to date that we are aware of has examined directional information flow between these regions, which was the primary aim of our study. Specifically, the current study aimed to understand how these three regions function as a network during anticipation of U-threat (and predictable threat/P-threat) in IP and AUD. Towards this goal, functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) were used to study inter-regional effective connectivities (ECs) and U- (and P-) threat-related modulations thereof within this network in two study samples. The first included a heterogeneous, transdiagnostic IP sample and a group of healthy controls (without any psychopathology). The second included groups of individuals with and without AUD diagnosis within the past two years who were otherwise matched on the rates of IPs. Within each study sample, parametric empirical Bayesian (PEB) modeling was used to conduct between-group differences in modulatory changes of ECs during U-threat and P-threat trials. In addition, we conducted exploratory analyses to determine whether any of the observed modulatory changes of ECs were associated with individual differences in anxiety and depressive symptoms (Study 1) or average weekly alcohol consumption in the past month (Study 2). Two main findings emerged: (Study 1) During U-threat trials, the right AM thalamus was more inhibited by the right AIC in individuals with IP relative to healthy controls; this directional influence was more prominent among participants who endorsed greater depressive, but not anxiety, symptoms; (Study 2) During U-threat trials, compared to the control group, the right AIC was more excited by the right AM thalamus in the AUD group; this directional influence was stronger among individuals who on average consumed more drinks per week. As expected, we found no group differences in modulatory changes of ECs during P-threat trials in either study sample. To our knowledge, this is the first study to examine directional interactions between key frontolimbic regions during anticipation of U-threat (and P-threat) and demonstrate the importance of top-down and bottom-up thalamic-insular projections during U-threat processing in IP and AUD, respectively. Prospective studies are warranted to examine causal pathways and establish temporal precedence

Liver cancer mortality and food consumption in Serbia, 1991–2010: An ecological study

© National Institute of Public Health, Prague 2016. Aim: This paper investigates the correlation between liver cancer mortality and consumption of food-groups in Serbia. Methods: We conducted an ecological study. The study comprised the population of the Republic of Serbia (about 7.5 million inhabitants) during the period 1991–2010. This ecological study included the data on food consumption per capita which were obtained by the Household Budget Survey and mortality data for liver cancer made available by the National Statistical Office. Linear trend model was used to assess a trend of age-adjusted liver cancer mortality rates (per 100, 000 persons) that were calculated by the method of direct standardization using the World Standard Population. Pearson correlation was performed to examine the association between liver cancer mortality and per capita food consumption quantified with a correlation coefficient (r value). Results: In Serbia, over the past two decades a significantly decreasing trend of liver cancer mortality rates has been observed (p < 0.001). Liver cancer mortality was significantly (p < 0.01) positively correlated with animal fat, beef, wine and spirits intake (r = 0.713, 0.631, 0.632 and 0.745, respectively). A weakly positive correlation between milk consumption and mortality from liver cancer (r = 0.559, p < 0.05) was found only among women. The strongest correlation was found between spirits consumption and liver cancer mortality rates in women (r = 0.851, p < 0.01). A negative correlation between coffee consumption and age-adjusted liver cancer mortality rates was found (r = −0.516, p < 0.05) only for the eldest men (aged 65 years or older). Conclusions: Correlations between liver cancer and dietary habits were observed and further effort is needed in order to investigate a possible causative association, using epidemiological analytical studies

Using Functional Near-Infrared Spectroscopy to Measure Effects of Delta 9-Tetrahydrocannabinol on Prefrontal Activity and Working Memory in Cannabis Users

Intoxication from cannabis impairs cognitive performance, in part due to the effects of Δ9-tetrahydrocannabinol (THC, the primary psychoactive compound in cannabis) on prefrontal cortex (PFC) function. However, a relationship between impairment in cognitive functioning with THC administration and THC-induced change in hemodynamic response has not been demonstrated. We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment. Eighteen adult regular cannabis users (final sample, n = 13) performed a working memory task (n-back) during fNIRS recordings, before and after receiving a single dose of oral synthetic THC (dronabinol; 20–50 mg). Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin (HbO) concentration after THC administration in several channels on the PFC during both the high working memory load (2-back) and the low working memory load (0-back) condition. The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS

Anterior insula activation during inhibition to smoking cues is associated with ability to maintain tobacco abstinence

Relapse to smoking after initial abstinence is a major clinical challenge with significant public health consequences. At the brain and behavioral level, those who relapse to tobacco smoking have both greater cue-reactivity and lower inhibitory control than those who remain abstinent. Little is known about neural activation during inhibitory control tasks in the presence of drug-related cues. In the current study, tobacco smokers (SMK; n = 22) and non-smoking controls (CON; n = 19) completed a Go/NoGo task involving smoking cues during a functional magnetic resonance imaging (fMRI) scan. Following the scan session, smokers were required to quit smoking, and maintenance of abstinence was evaluated as part of a 12-week smoking cessation trial. We evaluated pre-cessation brain activity during NoGo trials in smokers who were versus were not able to quit smoking. We then compared fMRI and inhibitory control measures between smokers and non-smokers. We did not find differences between SMK and CON in performance or activation to smoking or neutral cues. However, compared to SMK who relapsed, SMK who attained biochemically-validated abstinence at the end of the smoking cessation trial had greater neural activation in the anterior insula during NoGo trials specifically with smoking-related cues. Results indicate that within SMK, decreased inhibitory control activation during direct exposure to drug-related stimuli may be a marker of difficulty quitting and relapse vulnerability

Using Functional Near-Infrared Spectroscopy to Measure Effects of Delta 9-Tetrahydrocannabinol on Prefrontal Activity and Working Memory in Cannabis Users

Intoxication from cannabis impairs cognitive performance, in part due to the effects of Δ9-tetrahydrocannabinol (THC, the primary psychoactive compound in cannabis) on prefrontal cortex (PFC) function. However, a relationship between impairment in cognitive functioning with THC administration and THC-induced change in hemodynamic response has not been demonstrated. We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment. Eighteen adult regular cannabis users (final sample, n = 13) performed a working memory task (n-back) during fNIRS recordings, before and after receiving a single dose of oral synthetic THC (dronabinol; 20–50 mg). Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin (HbO) concentration after THC administration in several channels on the PFC during both the high working memory load (2-back) and the low working memory load (0-back) condition. The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS