Traditional active avoidance tasks have advanced the field of aversive learning and memory for decades and are useful for studying simple avoidance responses in isolation; however, these tasks have limited clinical relevance because they do not model several key features of clinical avoidance. In contrast, platform-mediated avoidance (PMA) more closely resembles clinical avoidance because the response i) is associated with an unambiguous safe location, ii) is not associated with an artificial termination of the warning signal, and iii) is associated with a decision-based appetitive cost. Recent findings on the neuronal circuits of PMA have confirmed that amygdala-striatal circuits are essential for avoidance. In PMA, however, the prelimbic cortex facilitates the avoidance response early during the warning signal, perhaps through disinhibition of the striatum. Future studies on avoidance should account for additional factors such as sex differences and social interactions that will advance our understanding of maladaptive avoidance contributing to neuropsychiatric disorders.

BACKGROUND: Chronic exposure to drugs of abuse disrupts frontostriatal glutamate transmission, which in turn meditates drug seeking. In animal models, N-Acetylcysteine normalizes dysregulated frontostriatal glutamatergic neurotransmission and prevents reinstated drug seeking; however, the effects of N-Acetylcysteine on human frontostriatal circuitry function and maintaining smoking abstinence is unknown. Thus, the current study tested the hypothesis that N-Acetylcysteine would be associated with stronger frontostriatal resting-state functional connectivity (rsFC), attenuated nicotine withdrawal and would help smokers to maintain abstinence over the study period.
METHODS: The present study examined the effects of N-Acetylcysteine on frontostriatal rsFC, nicotine-withdrawal symptoms and maintaining abstinence. Healthy adult, non-treatment seeking smokers (N=16; mean (SD) age 36.5±11.9; cigs/day 15.8±6.1; years/smoking 15.7±8.9) were randomized to a double-blind course of 2400mg N-Acetylcysteine (1200mg b.i.d.) or placebo over the course of 3½ days of monetary-incentivized smoking abstinence. On each abstinent day, measures of mood and craving were collected and participants attended a lab visit in order to assess smoking (i.e., expired-air carbon monoxide [CO]). On day 4, participants underwent fMRI scanning.
RESULTS: As compared to placebo (n=8), smokers in the N-Acetylcysteine group (n=8) maintained abstinence, reported less craving and higher positive affect (all p\'s<.01), and concomitantly exhibited stronger rsFC between ventral striatal nodes, medial prefrontal cortex and precuneus-key default mode network nodes, and the cerebellum [p<.025; FWE]).
CONCLUSIONS: Taken together, these findings suggest that N-Acetylcysteine may positively affect dysregulated corticostriatal connectivity, help to restructure reward processing, and help to maintain abstinence immediately following a quit attempt.

OBJECTIVE: We investigated whether volumetric differences in ADHD-associated brain regions are related to current symptoms of inattention and hyperactivity in healthy middle-aged adults and whether co-occurring anxiety/depression symptoms moderate these relationships.
METHODS: ADHD Self-Report Scale and Brief Patient Health Questionnaire were used to assess current symptoms of inattention, hyperactivity, anxiety, and depression in a population-based sample ( n = 269). Brain volumes, measured using a semi-automated method, were analyzed using multiple regression and structural equation modeling to evaluate brain volume-inattention/hyperactivity symptom relationships for selected regions.
RESULTS: Volumes of the left nucleus accumbens and a region overlapping the dorsolateral prefrontal cortex were positively associated with inattention symptoms. Left hippocampal volume was negatively associated with hyperactivity symptoms. The brain volume-inattention/hyperactivity symptom associations were stronger when anxiety/depression symptoms were controlled for.
CONCLUSIONS: Inattention and hyperactivity symptoms in middle-aged adults are associated with different brain regions and co-occurring anxiety/depression symptoms moderate these brain-behavior relationships.