Functional neuroanatomy of executive functions has been delineated in a large number of neuroimaging studies using conflict-inducing tasks. The neural basis of alcohol’s effects on cognitive control is poorly understood despite the evidence of impaired ability to evaluate competing demands and to inhibit maladaptive responses. In order to investigate effects of moderate intoxication, healthy social drinkers participated in both alcohol (0.60 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions while being scanned using blood oxygen level dependent (BOLD) fMRI. A modified 4-color Stroop task combined reading and color naming and used manual responses. Twenty subjects (10 women) were instructed to press a button corresponding to the font color except when a word was written in gray in which case they had to respond to the meaning of the word. Alcohol increased reaction times and a tendency to make more errors on incongruent trials. Behavioral indices of alcohol-induced premature responding correlated with the current drinking levels and impulsivity traits, suggesting an interaction between alcohol effects and personality predispositions. A distributed fronto-parietal cortical network was activated by incongruity. However, moderate alcohol inebriation selectively attenuated anterior cingulate cortex (ACC) activation during both high-conflict trials and erroneous responses, indicating vulnerability of the regulative function subserved by the ACC. By disrupting top-down, strategic processing, alcohol may interfere with goal-directed behavior, resulting in poor self control. The present results support models proposing that alcohol-induced prefrontal impairments diminish inhibitory control and are modulated by dispositional risk factors and levels of alcohol consumption.

When animals and their offspring are threatened, parents switch from self-defense to offspring protection. How self-defense is suppressed remains elusive. We postulated that suppression of the self-defense response, freezing, is gated via oxytocin acting in the centro-lateral amygdala (CeL). We found that rat dams conditioned to fear an odor, froze when tested alone, whereas if pups were present, they remained in close contact with them or targeted the threat. Furthermore, blocking oxytocin signaling in the CeL prevented the suppression of maternal freezing. Finally, pups exposed to the odor in the presence of the conditioned dam later froze when re-exposed alone. However, if oxytocin signaling in the dam had been blocked, pups failed to learn. This study provides a functional role for the well-described action of oxytocin in the central amygdala, and demonstrates that self-defense suppression allows for active pup protection and mother-pup interactions crucial for pup threat learning.DOI: http://dx.doi.org/10.7554/eLife.24080.001

Rationale Flexible behavior optimization relies on cognitive control which includes the ability to suppress automatic responses interfering with relevant goals. Extensive evidence suggests that the anterior cingulate cortex (ACC) is the central node in a predominantly frontal cortical network subserving executive tasks. Neuroimaging studies indicate that the ACC is sensitive to acute intoxication during conflict, but such evidence is limited to tasks using manual responses with arbitrary response contingencies. Objectives The present study was designed to examine whether alcohol's effects on top–down cognitive control would generalize to the oculomotor system during inhibition of hardwired saccadic responses. Methods Healthy social drinkers (N=22) underwent functional magnetic resonance imaging (fMRI) scanning and eye movement tracking during alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed visually guided prosaccades (PS) towards a target and volitional antisaccades (AS) away from it. To mitigate possible vasoactive effects of alcohol on the BOLD (blood oxygenation level-dependent) signal, resting perfusion was quantified with arterial spin labeling (ASL) and used as a covariate in the BOLD analysis. Results Saccadic conflict was subserved by a distributed frontoparietal network. However, alcohol intoxication selectively attenuated activity only in the ACC to volitional AS and erroneous responses. Conclusions This study provides converging evidence for the selective ACC vulnerability to alcohol intoxication during conflict across different response modalities and executive tasks, confirming its supramodal, high-level role in cognitive control. Alcohol intoxication may impair top–down regulative functions by attenuating the ACC activity, resulting in behavioral disinhibition and decreased self-control.

Neural circuits that allow for reciprocal communication between the brain and viscera are critical for coordinating behavior with visceral activity. At the same time, these circuits are positioned to convey signals from pathologic events occurring in viscera to the brain, thereby providing a structural basis for comorbid central and peripheral symptoms. In the pons, Barrington's nucleus and the norepinephrine (NE) nucleus, locus coeruleus (LC), are integral to a circuit that links the pelvic viscera with the forebrain and coordinates pelvic visceral activity with arousal and behavior. Here, we demonstrate that a prevalent bladder dysfunction, produced by partial obstruction in rat, has an enduring disruptive impact on cortical activity through this circuit. Within 2 weeks of partial bladder obstruction, the activity of LC neurons was tonically elevated. LC hyperactivity was associated with cortical electroencephalographic activation that was characterized by decreased low-frequency (1-3 Hz) activity and prominent theta oscillations (6 -8 Hz) that persisted for 4 weeks. Selective lesion of the LC-NE system significantly attenuated the cortical effects. The findings underscore the potential for significant neurobehavioral consequences of bladder disorders, including hyperarousal, sleep disturbances, and disruption of sensorimotor integration, as a result of central noradrenergic hyperactivity. The results further imply that pharmacological manipulation of central NE function may alleviate central sequelae of these visceral disorders.Barrington's nucleus ͉ bladder obstruction ͉ electroencephalographic activity ͉ locus coeruleus O veractive bladder is a prevalent disorder, affecting 17% of the population and negatively impacting quality of life (1). Partial bladder obstruction is a common cause of overactive bladder in males and is used to model overactive bladder in laboratory animals (2). Whereas the structural and functional changes induced in bladder by partial obstruction are well studied (3, 4), the impact on brain function has been neglected. The potential for central consequences of bladder dysfunctions exists because neural circuits are present that communicate pelvic visceral status to the brain so that behavior can be coordinated with visceral functions. Barrington's nucleus (the pontine micturition center) and the locus coeruleus (LC) are integral components of a circuit that performs this task (5). Barrington's nucleus neurons project to spinal preganglionic parasympathetic neurons, where they regulate activity of the bladder and other pelvic viscera (6). These projections form the efferent limb of the micturition reflex, in which Barrington's nucleus neurons are activated by bladder distention and in response, initiate bladder contraction (7). The same Barrington's nucleus neurons project to the LC, a major norepinephrine (NE)-containing nucleus with divergent efferent projections that densely innervate the forebrain (8, 9). Among its functions, the LC regulates arousal, shifts in attention, and involv...