Predicting Empathy From Resting State Brain Connectivity: A Multivariate Approach.

Recent task fMRI studies suggest that individual differences in trait empathy and empathic concern are mediated by patterns of connectivity between self-other resonance and top-down control networks that are stable across task demands. An untested implication of this hypothesis is that these stable patterns of connectivity should be visible even in the absence of empathy tasks. Using machine learning, we demonstrate that patterns of resting state fMRI connectivity (i.e. the degree of synchronous BOLD activity across multiple cortical areas in the absence of explicit task demands) of resonance and control networks predict trait empathic concern (n = 58). Empathic concern was also predicted by connectivity patterns within the somatomotor network. These findings further support the role of resonance-control network interactions and of somatomotor function in our vicariously driven concern for others. Furthermore, a practical implication of these results is that it is possible to assess empathic predispositions in individuals without needing to perform conventional empathy assessments

Your Resting Brain CAREs about Your Risky Behavior

Research on the neural correlates of risk-related behaviors and personality traits has provided insight into mechanisms underlying both normal and pathological decision-making. Task-based neuroimaging studies implicate a distributed network of brain regions in risky decision-making. What remains to be understood are the interactions between these regions and their relation to individual differences in personality variables associated with real-world risk-taking.We employed resting state functional magnetic resonance imaging (R-fMRI) and resting state functional connectivity (RSFC) methods to investigate differences in the brain's intrinsic functional architecture associated with beliefs about the consequences of risky behavior. We obtained an individual measure of expected benefit from engaging in risky behavior, indicating a risk seeking or risk-averse personality, for each of 21 participants from whom we also collected a series of R-fMRI scans. The expected benefit scores were entered in statistical models assessing the RSFC of brain regions consistently implicated in both the evaluation of risk and reward, and cognitive control (i.e., orbitofrontal cortex, nucleus accumbens, lateral prefrontal cortex, dorsal anterior cingulate). We specifically focused on significant brain-behavior relationships that were stable across R-fMRI scans collected one year apart. Two stable expected benefit-RSFC relationships were observed: decreased expected benefit (increased risk-aversion) was associated with 1) stronger positive functional connectivity between right inferior frontal gyrus (IFG) and right insula, and 2) weaker negative functional connectivity between left nucleus accumbens and right parieto-occipital cortex.Task-based activation in the IFG and insula has been associated with risk-aversion, while activation in the nucleus accumbens and parietal cortex has been associated with both risk seeking and risk-averse tendencies. Our results suggest that individual differences in attitudes toward risk-taking are reflected in the brain's functional architecture and may have implications for engaging in real-world risky behaviors

Rat Model of Pre-Motor Parkinson\u27s Disease: Behavioral and MRI Characterization.

Background: Parkinson\u27s disease (PD) is a chronic, progressive, neurodegenerative disorder with currently no known cure. PD has a significant impact on quality of life of the patients, as well as, the caregivers and family members. It is the second most common cause of chronic neurological disability in US and Europe. According to National Parkinson\u27s Foundation, there are almost 1 million patients in the Unites States and 50,000 to 60,000 new cases of PD are diagnosed each year. The total number of cases of PD is predicted to double by 2030. The annual cost associated with this disease is estimated to be $10.8 billion in the United States, including the cost of treatment and the cost of the disability. Although it is primarily thought of as a movement-disorder and is clinically diagnosed based on motor symptoms, non-motor symptoms such as cognitive and emotional deficits are thought to precede the clinical diagnosis by almost 20 years. By the time of clinical diagnosis, there is 80% loss in the dopamine content in the striatum and 50% degeneration of the substantia nigra dopamine cells. The research presented in this thesis was an attempt to develop an animal model of PD in its pre-motor stages. Such a model would allow us to develop pre-clinical markers for PD, and facilitate the development and testing of potential treatment strategies for the non-motor symptoms of the disorder. Specific Aims: There were five specific aims for this research: * The first specific aim dealt with development of a rat model of PD with slow, progressive onset of motor deficits, determination of timeline for future studies, and quantification the dopamine depletion in this model at a pre-motor stage. * The second and the third specific aims focused on testing for emotional (aversion) deficits and cognitive (executive functioning) deficits in this rat model at the 3 week timepoint determined during specific aim 1. * The fourth specific aim was to determine the brain network changes associated with the behavioral changes observed our rat model using resting state connectivity as a measure. * The fifth and the final specific aim was to test sodium butyrate, a drug from the histone deacetylase inhibitor family, as a potential treatment option for cognitive deficits in PD. Results: The 6-hydroxy dopamine based stepwise striatal lesion model of pre-motor PD, developed during this research, exhibits delayed onset of Parkinsonian gait like symptoms by week 4 after the lesions. At 3 weeks post lesion (3WKPD), the rats exhibit 27% reduction in striatal dopamine and 23%reduction in substantia nigra dopamine cells, with lack of any apparent motor deficits. The 3WKPD rats also exhibited changes in aversion. The fMRI study with the aversive scent pointed towards possible amygdala dysfunction sub-serving the aversion deficits. The executive function deficits tested using a rat analog of the Wisconsin card sorting test, divulged an extra-dimensional set shifting deficit in the 3WKPD rats similar to those reported in PD patients. The resting state connectivity study indicated significant changes in the 3WKPD rats compared to age matched controls. We observed increased overall connectivity of the motor cortex and increased CPu connectivity with prefrontal cortex, cingulate cortex, and hypothalamus in the 3WKPD rats compared to the controls. These observations parallel the observations in unmedicated early-stage PD patients. We also observed negative correlation between amygdala and prefrontal cortex as reported in humans. This negative correlation was lost in 3WKPD rats. Sodium butyrate treatment, tested in the cognitive deficit study, was able to ameliorate the extra-dimensional set shifting deficit observed in this model. This treatment also improved the attentional set formation. Conclusion: Taken together, our observations indicate that, the model of pre-motor stage PD developed during this research is a very high face validity rat model of late Braak stage 2 or early Braak stage 3 PD. Sodium butyrate was able to alleviate the cognitive deficits observed in our rat model. Hence, along with the prior reports of anti-depressant and neuroprotective effects of this drug, our results point towards a possible treatment strategy for the non-motor deficits of PD

Neural Markers of Individual Differences in Decision-making

In the last few years, neuroscientists have begun to identify associations between individual differences in decision-making and features of neuroanatomy and neurophysiology. Different tendencies in decision making, such as tolerance for risk, delay or effort, have been linked to various neurobiological measures, such as morphometry, structural connectivity, functional connectivity or the function of neurotransmitter systems. Though far from immutable, these neural features may nonetheless be suitable as relatively stable biomarkers for different decision traits. The establishment of such markers would achieve one of the stated goals of neuroeconomics, which is to improve the prediction of economic behavior across different contexts

Review: Non‐invasive brain stimulation in behavioral addictions: insights from direct comparisons with substance use disorders

Background and Objectives Treatment models developed for substance use disorders (SUDs) are often applied to behavioral addictions (BAs), even though the correspondence between these forms of addiction is unclear. This is also the case for noninvasive brain stimulation (NIBS) techniques being investigated as potential treatment interventions for SUDs and BAs. Objectives: to contribute to the development of more effective NIBS protocols for BAs. Methods Two literature searches using PubMed and Google Scholar were conducted identifying a total of 35 studies. The first search identified 25 studies examining the cognitive and neurophysiological overlap between BAs and SUDs. The second search yielded 10 studies examining the effects of NIBS in BAs. Results Impulsivity and cravings show behavioral and neurophysiologic overlaps between BAs and SUDs, however, other outcomes like working‐memory abilities or striatal connectivity, differ between BAs and SUDs. The most‐employed NIBS target in BAs was dorsolateral prefrontal cortex (DLPFC), which was associated with a decrease in cravings, and less frequently with a reduction of addiction severity. Conclusions and Scientific Significance Direct comparisons between BAs and SUDs revealed discrepancies between behavioral and neurophysiological outcomes, but overall, common and distinctive characteristics underlying each disorder. The lack of complete overlap between BAs and SUDs suggests that investigating the cognitive and neurophysiological features of BAs to create individual NIBS protocols that target risk‐factors associated specifically with BAs, might be more effective than transferring protocols from SUDs to BAs. Individualizing NIBS protocols to target specific risk‐factors associated with each BA might help to improve treatment interventions for BAs. (Am J Addict 2019;00:1–23

What role does the prefrontal cortex play in the processing of negative and positive stimuli in adolescent depression?

This perspective describes the contribution of the prefrontal cortex to the symptoms of depression in adolescents and specifically the processing of positive and negative information. We also discuss how the prefrontal cortex (PFC) activity and connectivity during tasks and at rest might be a biomarker for risk for depression onset in adolescents. We include some of our recent work examining not only the anticipation and consummation of positive and negative stimuli, but also effort to gain positive and avoid negative stimuli in adolescents with depression. We find, using region of interest analyses, that the PFC is blunted in those with depression compared to controls across the different phases but in a larger sample the PFC is blunted in the anticipatory phase of the study only. Taken together, in adolescents with depression there is evidence for dysfunctional PFC activity across different studies and tasks. However, the data are limited with small sample sizes and inconsistent findings. Larger longitudinal studies with more detailed assessments of symptoms across the spectrum are needed to further evaluate the role of the PFC in adolescent depression

Resting-State Theta Oscillations and Reward Sensitivity in Risk Taking

Females demonstrate greater risk aversion than males on a variety of tasks, but the underlying neurobiological basis is still unclear. We studied how theta (4–7 Hz) oscillations at rest related to three different measures of risk taking. Thirty-five participants (15 females) completed the Bomb Risk Elicitation Task (BRET), which allowed us to measure risk taking during an economic game. The Domain-Specific Risk-Taking Scale (DOSPERT) was used to measure self-assessed risk attitudes as well as reward and punishment sensitivities. In addition, the Barratt Impulsiveness Scale (BIS11) was included to quantify impulsiveness. To obtain measures of frontal theta asymmetry and frontal theta power, we used magnetoencephalography (MEG) acquired prior to task completion, while participants were at rest. Frontal theta asymmetry correlated with average risk taking during the game but only in the female sample. By contrast, frontal theta power correlated with risk taking as well as with measures of reward and punishment sensitivity in the joint sample. Importantly, we showed that reward sensitivity mediated a correlation between risk taking and the power of theta oscillations localized to the anterior cingulate cortex. In addition, we observed significant sex differences in source- and sensor-space theta power, risk taking during the game, and reward sensitivity. Our findings suggest that sensitivity to rewards, associated with resting-state theta oscillations in the anterior cingulate cortex, is a trait that potentially contributes to sex differences in risk taking

Overcoming Selfishness: Reciprocity, Inhibition, and Cardiac-Autonomic Control in the Ultimatum Game

The processes underlying decision-making in response to unfair offers in the ultimatum game (UG) have recently been discussed in light of models of reciprocity and fairness-related behavior. It has been suggested that behavior following norm-oriented, internalized expectations of reciprocity requires overcoming economic self-interest. In this study we investigated both, behavioral and peripheral-physiological indicators of inhibitory capacity related to neuronal networks that are likely to be involved in the behavioral response to unfair offers. Both heart-rate variability as an index of inhibitory capacity, and performance in a motor response inhibition task predicted rejection of unfair offers in an UG, suggesting an important role of inhibitory processes in overcoming economic temptations and regulating behavior conforming to social norms of reciprocity and fairness. The role of parasympathetic activity as a physiological trait-marker predicting inter-individual differences in the rejection of unfair offers is discussed

Physiological Correlates of Affective Decision-Making in Anxiety and Depression

Improving our understanding of cognitive and physiological profiles in anxiety and depression has the potential to reveal novel ways to target and improve treatments for these prevalent mental health conditions. The present study examined the impact of self-reported anxiety and depression symptoms on three established decision-making measures, the Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994), Balloon Analogue Risk Task (BART; Lejuez et al., 2002), and Game of Dice Task (GDT; Brand et al., 2005), in a diverse sample of 100 college students (age 18 to 35). Physiological measures of tonic heart rate variability and galvanic skin response were obtained to better characterize autonomic flexibility and sympathetic reactivity, respectively, during decision-making performance. Interoceptive sensitivity, measured via a heart beat perception task (Schandry, 1981), was also examined as a potential moderator in the relationship between sympathetic reactivity and decision-making. Consistent with the literature, BART performance was negatively associated with IGT performance, while GDT performance was positively associated with IGT performance. Contrary to our hypotheses, physiological measures did not distinguish individuals who reported anxiety and/or depression from those who did not. Of the three tasks, only IGT performance was associated with sympathetic reactivity. Consistent with our hypotheses, anxiety and greater sympathetic reactivity to losses in the task predicted better scores. Interoceptive sensitivity moderated the association between sympathetic reactivity and IGT performance, but only among those with anxiety, with better performance associated with a combination of lower interoceptive sensitivity and higher sympathetic reactivity. Low tonic HRV predicted worse IGT performance in depressed participants and worse GDT performance in anxious participants. These findings, though preliminary, have implications for treatment advances involving HRV biofeedback and interoceptive exposure. Our findings also highlight substantial differences between the IGT, BART, and GDT in their associations with anxiety, depression, and physiological markers, for consideration in cross study comparisons and future research