Neural Changes in Borderline Personality Disorder After Dialectical Behavior Therapy-A Review.

The biological component of the biosocial theory of emotion regulation stipulates that borderline personality disorder (BPD) arises from biological vulnerabilities to heightened emotional reactivity. Comprehensive reviews have consistently implicated abnormalities in the amygdala, anterior cingulate cortex, and hippocampus in the neurobiology of BPD. While Dialectical Behavior Therapy (DBT) is the leading evidence-based psychotherapy for the treatment of BPD, there remains a paucity of literature examining changes in the neurobiology of BPD following DBT treatment. Nine studies were identified that examined neurobiological changes in BPD after the completion of DBT. Results indicated that there was significant deactivation of amygdala activity as well as the anterior cingulate cortex in patients with BPD after DBT treatment. As well, several studies found after DBT treatment, BPD patients had a decreased activity in the inferior frontal gyrus in response to arousing stimuli and increased activity in response to inhibitory control. Future research on the neurobiological change after DBT treatment can help clarify biological mechanisms of change in BPD.

Neurocognitive decision-making processes of casual methamphetamine users.

Neuroadaptations caused by chronic methamphetamine (MA) use are likely major contributors to high relapse rate following treatment. Thus, focusing intervention efforts at pre-empting addiction in vulnerable populations, thereby preventing MA-use-induced neurological changes that make recovery so challenging, may prove more effective than targeting chronic users. One approach is studying casual/recreational users, not diagnosed with substance use disorder. This group may be at high risk for addiction due to their experience with MA. On the other hand, they may be resilient against addiction since they were able to maintain casual use over the years and not become addicted. Understanding their neuro-cognitive characteristics during decision-making and risk-taking would help solve this dilemma and, may help identify intervention strategies. Unfortunately, research on neuro-cognitive characteristics of casual MA users is currently lacking. In this work we begin to address this deficit. This study was part of a larger investigation of neural correlates of risky sexual decision-making in men who have sex with men. While undergoing functional magnetic resonance imaging, 31 casual MA users and 66 non-users performed the CUPS task, in which they decided to accept or refuse a series of mixed gambles. Convergent results from whole brain, region of interest and psychophysiological interaction (PPI) analyses are presented. Whole brain analysis identified an amygdala-striatal cluster with weaker activation in casual MA users compared to non-users during decision-making. Activity in that cluster inversely correlated with decisions to gamble: lower activation corresponded to higher risk taking. Using this cluster as a seed in PPI analyses, we identified a wide range of neural network differences between casual MA users and non-users. Parametric whole brain analyses identified clusters in the ventral striatum, posterior insula and precuneus where activations modulated by risk and reward were significantly weaker in casual MA users than in non-users. The striatal cluster identified in these analyses overlapped with the amygdala-striatal cluster. This work identified neural differences in casual MA users' reward processing and outcome learning systems which may underlie their increased real-world risk-taking. It suggests that while making decisions casual MA users focus primarily on potential gain unlike non-users who also take the riskiness of the choice into consideration.

Prefrontal Cortical Activity During the Stroop Task: New Insights into the Why and the Who of Real-World Risky Sexual Behavior.

Background: Research suggests that deficits in both executive functioning and trait impulsivity may play a role in risky sexual behavior. At the neural level, differences in regulation of the prefrontal cortex have been linked to impulsivity, measured neurocognitively and through self-report. The relationship between neurocognitive measures of executive control and trait impulsivity in predicting risky sexual behavior has not been investigated. Purpose: To investigate the relationship between neural functioning during the Stroop task and risky sexual behavior, as well as the effect of individual differences in urgent (positive and negative) impulsivity on this relationship. Methods: A total of 105 sexually active men who have sex with men completed the Stroop task during functional magnetic resonance imaging scanning. They also completed impulsivity inventories and self-reported their risky sexual behavior (events of condomless anal sex in the last 90 days). Results: Risky participants had greater activation than safe participants during the color congruent condition of the Stroop task in anterior cingulate cortex/dorsomedial prefrontal cortex, dorsolateral prefrontal cortex, left frontal pole, and right insula. Across these regions, this neural activation mediated the link between (positive and/or negative) urgent impulsivity and risky sexual behavior. Conclusions: Findings suggest that the brains of men who engage in risky sexual behavior may employ a different distribution of cognitive resources during tasks of executive functioning than men who practice safe sex, and that this may relate to differences in the prefrontal cortical/fronto-insular system responsible for impulse control.

The role of the dorsal anterior insula in sexual risk: Evidence from an erotic Go/NoGo task and real-world risk-taking.

The insula plays an important role in response inhibition. Most relevant here, it has been proposed that the dorsal anterior insular cortex (dAIC) plays a central role in a salience network that is responsible for switching between the default mode network and the executive control network. However, the insula's role in sexually motivated response inhibition has not yet been studied. In this study, eighty-five 18- to 30-year-old sexually active men who have sex with men (MSM) performed an erotic Go/NoGo task while in an MRI scanner. Participants' real-world sexual risk-taking (frequency of condomless anal intercourse over the past 90 days) was then correlated with their neural activity during the task. We found greater activity in bilateral anterior insular cortex (both dorsal and ventral) on contrasts with stronger motivational information (attractive naked male pictures versus pictures of clothed, middle-aged females) and on contrasts requiring greater response inhibition (NoGo versus Go). We also found that activity in the right dAIC was negatively correlated with participants' real-world sexual risk-taking. Our results confirmed the involvement of the insular cortex in motivated response inhibition. Especially, the decreased right dAIC activity may reduce the likelihood that the executive control network will come online when individuals are faced with situations requiring inhibitory control and thus lead them to make more risky choices.

Virtually 'in the heat of the moment': insula activation in safe sex negotiation among risky men.

HIV is most prevalent among men who have sex with men (MSM), and although most MSM use condoms consistently during casual sex, some take risks. To better understand the psychology of those risky decisions, we examined neural correlates of playing a virtual sexual 'hook up' game in an functional magnetic resonance imaging scanner in MSM who had, in the past 90 days, been sexually risky (N = 76) or safe (N = 31). We found that during potentially risky sexual choices, previously risky MSM had more right insula activity than previously safe MSM. Real-life sexual risk was related to trait positive and negative urgency. Insula activity that differentiated risky and safe MSM was related to trait positive and negative urgency. Future work should further examine if, and to what extent, insula activation during safe sex negotiation drives MSM's rash risky sexual decision-making.

Influential Mutations in the SMAD4 Trimer Complex Can Be Detected from Disruptions of Electrostatic Complementarity.

This article examines three techniques for rapidly assessing the electrostatic contribution of individual amino acids to the stability of protein-protein complexes. Whereas the energetic minimization of modeled oligomers may yield more accurate complexes, we examined the possibility that simple modeling may be sufficient to identify amino acids that add to or detract from electrostatic complementarity. The three methods evaluated were (a) the elimination of entire side chains (e.g., glycine scanning), (b) the elimination of the electrostatic contribution from the atoms of a side chain, called nullification, and (c) side chain structure prediction using SCWRL4. These techniques generate models in seconds, enabling large-scale mutational scanning. We evaluated these techniques on the SMAD2/SMAD4 heterotrimer, whose formation plays a crucial role in antitumor pathways. Many studies have documented the clinical and structural effect of specific mutations on trimer formation. Our results describe how glycine scanning yields more specific predictions, although nullification may be more sensitive, and how side chain structure prediction enables the identification of uncharged-to-charge mutations.

Eye blink rate predicts reward decisions in adolescents.

The ventral striatum displays hyper-responsiveness to reward in adolescents relative to other age groups, and animal research on the developmental trajectory of the dopaminergic system suggests that dopamine may underlie adolescent sensitivity to reward. However, practical limitations prevent the direct measurement of dopamine in healthy adolescents. Eye blink rate (EBR) shows promise as a proxy measure of striatal dopamine D2 receptor function. We investigated developmental differences in the relationship between EBR and reward-seeking behavior on a risky decision-making task. Increasing EBR was associated with greater reward maximization on the task for adolescent but not adult participants. Furthermore, adolescents demonstrated greater sensitivity to reward value than adults, as evinced by shifts in decision patterns based on increasing potential reward. These findings suggest that previously observed adolescent behavioral and neural hypersensitivity to reward may in fact be due to greater dopamine receptor activity, as represented by the relationship of blink rate and reward-seeking behavior. They also demonstrate the feasibility and utility of using EBR as a proxy for dopamine in healthy youth in whom direct measurements of dopamine are prohibitively invasive.

Neural representation of expected value in the adolescent brain.

Previous work shows that the adolescent reward system is hyperactive, but this finding may be confounded by differences in how teens value money. To address this, we examined the neural ontogeny of objective value representation. Adolescent and adult participants performed a monetary gambling task in which they chose to accept or reject gambles of varying expected value. Increasing expected value had a stronger influence over gambling choices in adolescents relative to adults, an effect that was paralleled by greater activation in the ventral striatum in adolescents. This unique adolescent ventral striatum response remained even after matching groups on acceptance behavior. These behavioral and neural data suggest that the value of available options has a greater influence in adolescent versus adult choices, even when objective value and subjective choice are held constant. This research provides further evidence that hyperactivation of reward circuitry in adolescence may be a normative ontogenetic shift that is due to greater valuation in the adolescent brain.

Behavioral and neural correlates of loss aversion and risk avoidance in adolescents and adults.

Individuals are frequently faced with risky decisions involving the potential for both gain and loss. Exploring the role of both potential gains and potential losses in predicting risk taking is critical to understanding how adolescents and adults make the choice to engage in or avoid a real-life risk. This study aimed to examine the impact of potential losses as well as gains on adolescent decisions during risky choice in a laboratory task. Adolescent (n=18) and adult (n=16) participants underwent functional magnetic resonance imaging (fMRI) during a mixed gambles task, and completed questionnaires measuring real-world risk-taking behaviors. While potential loss had a significantly greater effect on choice than potential gain in both adolescents and adults and there were no behavioral group differences on the task, adolescents recruited significantly more frontostriatal circuitry than adults when choosing to reject a gamble. During risk-seeking behavior, adolescent activation in medial prefrontal cortex (mPFC) was negatively correlated with self-reported likelihood of risk taking. During risk-avoidant behavior, mPFC activation of in adults was negatively correlated with self-reported benefits of risk-taking. Taken together, these findings reflect different neural patterns during risk-taking and risk-avoidant behaviors in adolescents and adults.

The relationship between measures of impulsivity and alcohol misuse: an integrative structural equation modeling approach.

BACKGROUND: Higher levels of impulsivity have been implicated in the development of alcohol use disorders. Recent findings suggest that impulsivity is not a unitary construct, highlighted by the diverse ways in which the various measures of impulsivity relate to alcohol use outcomes. This study simultaneously tested the following dimensions of impulsivity as determinants of alcohol use and alcohol problems: risky decision making, self-reported risk-attitudes, response inhibition, and impulsive decision making. METHODS: Participants were a community sample of nontreatment seeking problem drinkers (n = 158). Structural equation modeling (SEM) analyses employed behavioral measures of impulsive decision making (delay discounting task [DDT]), response inhibition (stop signal task [SST]), and risky decision making (Balloon Analogue Risk Task [BART]), and a self-report measure of risk-attitudes (domain-specific risk-attitude scale [DOSPERT]), as predictors of alcohol use and of alcohol-related problems in this sample. RESULTS: The model fits well, accounting for 38% of the variance in alcohol problems, and identified 2 impulsivity dimensions that significantly loaded onto alcohol outcomes: (i) impulsive decision making, indexed by the DDT; and (ii) risky decision making, measured by the BART. CONCLUSIONS: The impulsive decision-making dimension of impulsivity, indexed by the DDT, was the strongest predictor of alcohol use and alcohol pathology in this sample of problem drinkers. Unexpectedly, a negative relationship was found between risky decision making and alcohol problems. The results highlight the importance of considering the distinct facets of impulsivity to elucidate their individual and combined effects on alcohol use initiation, escalation, and dependence.