Freezing suppression by oxytocin in central amygdala allows alternate defensive behaviours and mother-pup interactions.

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.

Effects of acute alcohol intoxication on saccadic conflict and error processing.

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.

Acute alcohol intoxication impairs top-down regulation of Stroop incongruity as revealed by blood oxygen level-dependent functional magnetic resonance imaging.

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. To investigate the 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) functional magnetic resonance imaging (fMRI). A modified four-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 frontoparietal 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.

Effects of Alcohol Intoxication on Response Conflict in a Flanker Task.

Events evoke seamlessly integrated stimulus evaluation and response preparation processing streams, guided by regulative functions that change behavior flexibly in accord with the internal goals and contextual demands. The neural basis of the effects of alcohol intoxication on these processing streams is poorly understood, despite the evidence of alcohol's deleterious effects on both attention and motor control. In an attempt to separate and examine relative susceptibility of these two dimensions, we employed a color version of the Eriksen flanker task that manipulated compatibility at the stimulus- and response-processing levels. Functional magnetic resonance imaging (fMRI) was performed in healthy social drinkers as they participated in both alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. Alcohol increased reaction times to response-level incongruity and decreased accuracy overall. Relative to the no-conflict condition, the observed brain activity was predominantly evoked by response-related conflict in medial prefrontal and lateral prefrontal cortices under placebo, in agreement with extensive evidence of their role in conflict processing. Activity evoked by response incongruity in the medial frontal cortex and insula was insignificant under alcohol, indicating its interference with response inhibition and preparation. Conversely, activity in ventrolateral prefrontal and premotor areas was relatively greater under alcohol than placebo, suggesting their compensatory engagement. This finding is consistent with the compensatory prefrontal activity increase found in studies with chronic alcoholic individuals, indicating functional reorganization with a goal of optimizing response strategy. These results delineate functional differences and selective susceptibility of a prefrontal network subserving response-level conflict processing. Our findings are incompatible with notions that moderate alcohol primarily affects attentional or stimulus-related processing and argue instead that its primary influence is on response inhibition, selection, and execution, with ramifications for the models of behavioral self-control and the inability to refrain from drinking.

Effects of alcohol intoxication and gender on cerebral perfusion: an arterial spin labeling study.

An increasing number of studies use functional MRI (fMRI) and blood oxygen level-dependent (BOLD) signal to investigate the neurofunctional basis of acute alcohol effects on the brain. However, the BOLD signal reflects neural activity only indirectly as it depends on regional hemodynamic changes and is therefore sensitive to vasoactive substances, such as alcohol. We used MRI-based pulsed arterial spin labeling (ASL) method to quantify effects of acute intoxication on resting cerebral perfusion. Gender effects have not been previously examined and yet they are of particular interest given the differences in hormonal dynamics, alcohol metabolism, and hemodynamic regulation. Nineteen young, healthy individuals (nine women) with no personal or familial alcohol- or drug-related problems served as their own controls by participating in both alcohol (0.6g/kg ethanol for men, 0.55g/kg for women) and placebo scanning sessions in a counterbalanced manner. Regionally specific effects of the moderate alcohol dose on gray matter perfusion were examined with voxel-wise and region-of-interest analyses suggesting an interaction between gender and alcohol beverage. Acute intoxication increased perfusion in bilateral frontal regions in men but not in women. Under placebo, stronger cortical perfusion was observed in women compared with men primarily in the left hemisphere in frontal, parietal, and temporal areas. These results emphasize gender differences and regional specificity of alcohol's effects of cerebral perfusion possibly because of interactive influences on hormonal, metabolic, and hemodynamic autoregulatory systems. Alcohol-induced perfusion increase correlated positively with impulsivity/antisocial tendencies, consistent with dopaminergic mediation of reward, and its effects on cortical perfusion. Additional ASL studies are needed to investigate dose- and time-dependent effects of alcohol intoxication and gender on the hemodynamic factors that conjointly influence BOLD signal to disambiguate the vascular/metabolic mechanisms from the neurally based changes.

Impact of overactive bladder on the brain: central sequelae of a visceral pathology.

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.