Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertainty-related expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

In this paper we provide a focused review of the literature examining neural mechanisms involved in cognitive control over memory processes that can influence, and in turn are influenced by, emotional processes. The review is divided into two parts, the first focusing on working memory and the second on long-term memory. With regard to working memory, we discuss the neural bases of (1) control mechanisms that can select against distracting emotional information, (2) mechanisms that can regulate emotional reactions or responses, (3) how mood state influences cognitive control, and (4) individual differences in control mechanisms. For long-term memory, we briefly review (1) the neural substrates of emotional memory, (2) the cognitive and neural mechanisms that are involved in controlling emotional memories and (3) how these systems are altered in post-traumatic stress disorder. Finally, we consider tentative generalizations that can be drawn from this relatively unexplored conjunction of research endeavors.

Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.

The capacity to anticipate aversive circumstances is central not only to successful adaptation but also to understanding the abnormalities that contribute to excessive worry and anxiety disorders. Forecasting and reacting to aversive events mobilize a host of affective and cognitive capacities and corresponding brain processes. Rapid event-related functional magnetic resonance imaging (fMRI) in 21 healthy volunteers assessed the overlap and divergence in the neural instantiation of anticipating and being exposed to aversive pictures. Brain areas jointly activated by the anticipation of and exposure to aversive pictures included the dorsal amygdala, anterior insula, dorsal anterior cingulate cortex (ACC), right dorsolateral prefrontal cortex (DLPFC), and right posterior orbitofrontal cortex (OFC). Anticipatory processes were uniquely associated with activations in rostral ACC, a more superior sector of the right DLPFC, and more medial sectors of the bilateral OFC. Activation of the right DLPFC in anticipation of aversion was associated with self-reports of increased negative affect, whereas OFC activation was associated with increases in both positive and negative affect. These results show that anticipation of aversion recruits key brain regions that respond to aversion, thereby potentially enhancing adaptive responses to aversive events.

Lack of volition is a key feature of depression. Integrally tied to other symptoms of depression, avolition importantly contributes to the symptom heterogeneity, variations in disease course, and differential treatment response that charactenize mood disorders. The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) have prominent and distinct roles in volition, particularly in the formation and implementation of action plans. Cognitive control and conflict monitoring of internal and external cues are central domains of DLPFC and ACC function that are recruited during volition. Depressed individuals frequently hypoactivity in these two cortical regions, which may explain the lack of volition that frequently accompanies depression. Accordingly, cognitive deficits in the organization and allocation of resources, as well as decreased engagement in goal-directed behaviors, likely reflect deficient functioning of the DLPFC and ACC. Increased attention to volition in research on depression may further inform efforts to uncover the neurobiology and pathophysiology of the disorder and, in turn, improve on current treatment options.The heterogeneity of symptoms in depression has been a critical confound in our attempts to understand and successfully treat individuals with it. As a result, the etiology and pathophysiology of depression remains elusive. The cardinal features of sad mood and loss of interest or pleasure have not been particularly heterogeneity in depression, affected individuals experience lack of volition to varying degrees, which may correspond, to the replicated finding that a subgroup of depressed patients actually show increased ventral ACC activity before treatment and that the amount of pretreatment ventral ACC activity is directly proportional to the degree of eventual treatment response. Thus, individuals with depression are an excellent research population for surveying individual differences in volition across a broad range of its expression.Increased integration of depression and volition research may further inform the pathophysiology of the disorder and viable treatment options. Avolition as a symptom of depression could be directly attacked using biological or psychological interventions that target the DLPFC and the ACC and their respective functions in cognitive control and conflict monitoring. In addition, mental health care providers could capitalize on the preserved volition that exists in some patients, an issue that is not widely appreciated. In sum, serious consideration of volition could contribute significantly to mitigating the tremendous personal suffering and societal burden associated with depression.

The present study was undertaken to determine whether aversiveness contributes to startle potentiation in anticipation of affective pictures above and beyond the effects of emotional arousal. Further, participants high in trait anxious apprehension, which is characterized by worry about the future, were expected to show especially pronounced anticipatory startle responses. Startle blink reflex was measured during warning stimuli that predicted the valence of ensuing aversive/unpleasant, pleasant, or neutral pictures. Startle magnitude was larger in anticipation of aversive than of pleasant pictures and smallest in anticipation of neutral pictures. Enhanced startle potentiation was not found in anxious apprehension subjects. These data suggest that the aversive nature of stimuli contribute to the potentiation of startle above and beyond the effects of emotional arousal, which may be a universal phenomenon not modulated by individual differences.