A Review of Preclinical Studies to Understand Fear During Adolescence

The most rapid physical and psychological growth occurs during adolescence, a period of transition from childhood to adulthood when the incidence of anxiety disorder peaks in humans. Human and animal studies suggest that dramatic changes in prefrontal cortical areas during adolescence are responsible for such prevalence of anxiety. Only recently, however, has the relationship between prefrontal immaturity and differential fear processing across adolescence been directly and systematically examined. Such progress is largely due to the culmination of rodent studies that delineated the fear learning, expression, and inhibition neural circuitry, and preclinical studies that provided avenues for translation. This article summarises those initial findings on the circuitry of fear inhibition, and describes in detail the new findings on adolescent fear inhibition that highlight the prefrontal cortex as a key, unrefined brain region that may govern adolescent vulnerability to anxiety disorders. Specifically, adolescent rodents have been demonstrated to be impaired in inhibiting learned fear responses following fear extinction due to prefrontal immaturity, a discovery that was shortly after replicated in adolescent humans (at least the behavioural component). Our desire for this article is to acquaint both research and clinical psychologists with the neural circuitry of fear learning and extinction, turn the attention to developmental work, and facilitate translation of preclinical rodent findings in humans.     

Online monitoring of the social presence effects in a two‐person‐like driving video game using near‐infrared spectroscopy

We examined how a friend's presence affects a performer's prefrontal activation in daily‐life activities using two wireless portable near‐infrared spectroscopy (NIRS) devices. Participants played a driving video game either solely in the single group or with a friend in the paired group. The two groups (single and paired) were subdivided according to their game proficiency (low and high). The NIRS data demonstrated a significant interaction of group by proficiency. Low‐proficiency players in the paired group showed lower activation than those in the single group, but high‐proficiency players did not. In the paired group, high‐proficiency players showed higher activation than low‐proficiency players, but not in the single group. These results suggest that NIRS detects social presence effects in everyday situations: decreasing prefrontal activation in low‐proficiency performers due to tension reduction and increasing prefrontal activation in high‐proficiency performers due to increased arousal.     

The modulatory impact of reward and attention on global feature selection in human visual cortex

Reward powerfully influences human behaviour and perception, with reward effects being observed already on the level of basic sensory processing. Although reward-related modulations generally resemble those related to attentional selection, it is debated whether these effects indeed reflect the same selection operations. Here we focus on neuromagnetic indices of global colour-based attention in visual cortex, and ask whether reward elicits the same or separable underlying modulation effects. Observers performed a colour/orientation selection task where colour served to define the target as well as reward prospect. On each trial a target containing the target colour and one other colour was presented in the left visual field (VF) together with a bicoloured distractor in the right VF. Reward was delivered on correctly performed trials when the reward colour appeared in the target but not when it appeared in the distractor. The effect of global colour selection was assessed by comparing the brain response to the distractor depending on whether it contained the target colour, the reward colour, both, or neither. We observed that both the reward and target colour led to similar increases of the neuromagnetic response between ~200–260 ms originating from the same ventral extrastriate visual cortex areas, albeit slightly temporally lagged. Importantly, the response to the target and reward colour alone always added up to match the response size of their combined presentation. These results suggest that while reward and attention recruit the same global feature selection effects in extrastriate visual cortex, they are likely controlled by independent top-down influences.     

Stress,coping, executive function,and brain activation in adolescent offspring of depressed and nondepressed mothers

This study examined the associations among chronic stress, activation in the prefrontal cortex (PFC), executive function, and coping with stress in at-risk and a comparison sample of adolescents. Adolescents (N = 16; age 12–15) of mothers with (n = 8) and without (n = 8) a history of depression completed questionnaires, neurocognitive testing, and functional neuroimaging in response to a working memory task (N-back). Children of depressed mothers demonstrated less activation in the anterior PFC (APFC) and both greater and less activation than controls in distinct areas within the dorsal anterior cingulate cortex (dACC) in response to the N-back task. Across both groups, activation of the dorsolateral PFC (DLPFC; Brodmann area [BA9]) and APFC (BA10) was positively correlated with greater exposure to stress and negatively correlated with secondary control coping. Similarly, activation of the dACC (BA32) was negatively correlated with secondary control coping. Regression analyses revealed that DLPFC, dACC, and APFC activation were significant predictors of adolescents’ reports of their use of secondary control coping and accounted for the effects of stress exposure on adolescents’ coping. This study provides evidence that chronic stress may impact coping through its effects on the brain regions responsible for executive functions foundational to adaptive coping skills.     

Incidental regulation of attraction: The neural basis of the derogation of attractive alternatives in romantic relationships

Although a great deal of research addresses the neural basis of deliberate and intentional emotion-regulation strategies, less attention has been paid to the neural mechanisms involved in implicit forms of emotion regulation. Behavioural research suggests that romantically involved participants implicitly derogate the attractiveness of alternative partners, and the present study sought to examine the neural basis of this effect. Romantically committed participants in the present study were scanned with functional magnetic resonance imaging (fMRI) while indicating whether they would consider each of a series of attractive (or unattractive) opposite-sex others as a hypothetical dating partner both while under cognitive load and no cognitive load. Successful derogation of attractive others during the no cognitive load compared to the cognitive load trials corresponded with increased activation in the ventrolateral prefrontal cortex (VLPFC) and posterior dorsomedial prefrontal cortex (pDMPFC), and decreased activation in the ventral striatum, a pattern similar to those reported in deliberate emotion-regulation studies. Activation in the VLPFC and pDMPFC was not significant in the cognitive load condition, indicating that while the derogation effect may be implicit, it nonetheless requires cognitive resources. Additionally, activation in the right VLPFC correlated with participants' level of relationship investment. These findings suggest that the RVLPFC may play a particularly important role in implicitly regulating the emotions that threaten the stability of a romantic relationship.     

A model of amygdala–hippocampal–prefrontal interaction in fear conditioning and extinction in animals

Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animals learn physiological (e.g. heart rate) and behavioral (e.g. freezing) responses to stimuli that have been paired with a highly aversive event (e.g. electrical shock). The key feature of our model is that learning of these conditioned responses in the central nucleus of the amygdala is modulated by two separate processes, one from basolateral amygdala and signaling a positive prediction error, and one from the vmPFC, via the intercalated cells of the amygdala, and signaling a negative prediction error. In addition, we propose that hippocampal input to both vmPFC and basolateral amygdala is essential for contextual modulation of fear acquisition and extinction. The model is sufficient to account for a body of data from various animal fear conditioning paradigms, including acquisition, extinction, reacquisition, and context specificity effects. Consistent with studies on lesioned animals, our model shows that damage to the vmPFC impairs extinction, while damage to the hippocampus impairs extinction in a different context (e.g., a different conditioning chamber from that used in initial training in animal experiments). We also discuss model limitations and predictions, including the effects of number of training trials on fear conditioning.     

Using transcranial magnetic stimulation methods to probe connectivity between motor areas of the brain

Transcranial magnetic stimulation is increasingly used as a tool to explore cortical motor function in healthy subjects and in patients with neurological disease or injury. This review describes a “twin coil” TMS approach that allows investigation of time related changes in functional connectivity between primary motor cortex and other areas in preparation for a forthcoming movement. Investigations into premotor–motor interactions show that these are specific to the type of task that is performed as well as the muscles used to control the movement, allowing us to monitor information flow within motor networks with millisecond time resolution.