Neural activity associated with monitoring the oscillating threat value of a tarantula

Abstract

Phylogenetic threats such as spiders evoke our deepest primitive fears. When close or looming, such threats engage evolutionarily conserved monitoring systems and defense reactions that promote self-preservation. With the use of a modified behavioral approach task within functional MRI, we show that, as a tarantula was placed closer to a subject's foot, increased experiences of fear coincided with augmented activity in a cascade of fear-related brain networks including the periaqueductal gray, amygdala, and bed nucleus of the stria terminalis. Activity in the amygdala was also associated with underprediction of the tarantula's threat value and, in addition to the bed nucleus of the stria terminalis, with monitoring the tarantula's threat value as indexed by its direction of movement. Conversely, the orbitofrontal cortex was engaged as the tarantula grew more distant, suggesting that this region emits safety signals or expels fear. Our findings fractionate the neurobiological mechanisms associated with basic fear and potentially illuminate the perturbed reactions that characterize clinical phobias.expectancy errors | imminence | distance E volutionary pressures have selected for mechanisms that encourage the avoidance of close or looming threat (1-3). In humans, this innate capacity is particularly evident with phylogenetic threats such as spiders, which rate among the most ubiquitous of phobias (4). For example, in everyday life it is common to experience a primal surge of terror when a spider crawls within our personal space, yet we may observe a distant spider without trepidation. In the clinical setting, behavioral approach tasks are used to expose phobic patients to phobogenic stimuli (e.g., spiders or snakes) at varying distances to evaluate and treat their fear responses. Such approaching threats elicit precipitous increases in subjective fear and autonomic arousal (5, 6), which are characteristics of the exaggerated emotional responses observed in phobic subjects.Research in rodents has shown that encountering a distant or close natural predator (e.g., a cat) evokes distinct defense reactions in the form of behavioral quiescence and vigorous flight, respectively (7). In humans, functional neuroimaging has begun to reveal the brain networks implicated in such situations of immediate danger. One study showed that the active avoidance of an artificial predator with the ability to chase, capture, and inflict pain resulted in brain activity switching from ventromedial prefrontal cortex to the midbrain, including the periaqueductal gray (PAG), as the threat became more imminent (8). Two recent studies have also shown that tracking the increasing proximity of a shock stimulus is associated with activity in the bed nucleus of the stria terminalis (BNST), a region highly connected to the amygdala (9), whereas courage associated with self-administered movement of a snake toward the subject's own head increases activating the ventromedial prefrontal cortex (10). These studies point to an anatomical network involved ...

Attachment figures activate a safety signal-related neural region and reduce pain experience

“…The present investigation examined the hypothesis that an attachment figure may act as a safety signal during a threatening experience, relying on neural regions known to be involved in signaling safety and reducing distress or threat. Consistent with this analysis, we found that viewing an attachment figure (romantic partner) during an experience of physical pain led to greater activity in the VMPFC, a region implicated in safety signaling and fear extinction (10)(11)(12)(13)(14)(15)(16), and attenuated reports of pain and pain-related neural activity. Specifically, we found that viewing partner pictures while receiving pain led to lower pain ratings than viewing control pictures while receiving pain, particularly during the high-pain trials.…”

“…Thus, in rats, stimulating the VMPFC while presenting a fearinducing cue diminishes fear responding, suggesting a role for this region in inhibiting the fear response (18). Similarly, in humans, increased activity in the VMPFC (including the subgenual anterior cingulate cortex; subACC) has been observed in response to safety signals (relative to fear-predictive stimuli) (11)(12)(13)(14), and greater activity in the VMPFC/subACC during fear extinction or learned safety has been associated with reduced fear responding (reductions in skin conductance) (14). Thus, in the context of fear learning, VMPFC activity appears to track stimuli that signal safety, and this activity is thought to modulate other neural regions that are involved in responding to the threat at hand.…”

“…Thus, in rats, stimulating the VMPFC while presenting a fearinducing cue diminishes fear responding, suggesting a role for this region in inhibiting the fear response (18). Similarly, in humans, increased activity in the VMPFC (including the subgenual anterior cingulate cortex; subACC) has been observed in response to safety signals (relative to fear-predictive stimuli) (11)(12)(13)(14), and greater activity in the VMPFC/subACC during fear extinction or …”

“…Although we do not view safety-signaling processes as being incompatible with reward-related processes, because cues of safety may themselves be experienced as rewarding (16,32), it is important to explore whether the current task activates neural regions that are more common to studies of safety signaling or more common to studies exploring the rewarding experience of viewing partner pictures. Specifically, research on safety-signaling and fear-extinction processes typically have yielded VMPFC activity without other reward-related regions such as the ventral striatum (11)(12)(13)(14) and have shown that the ventral striatum is not needed for safety-signaling processes (33) On the other hand, previous work on viewing romantic partners has led to increased activity in dopamine-rich reward-related regions, such as the caudate and ventral tegmental area, but not to activity in the VMPFC (34)(35)(36)(37)(38). Thus, exploring the pattern of neural activity associated with viewing attachment figures during pain would help determine if this experience is more closely aligned with safetysignaling processes or more closely aligned with the potentially rewarding experience of viewing partner pictures.…”

Behavioral and neuroimaging responses induced by mental imagery of threatening scenarios

“…In short, they have shown that distant or potential threats are associated with activity in the ventromedial prefrontal cortex (vmPFC), but as the threat becomes nearer and intense, brain activity shifts to the PAG [13][14][15]. In these experiments, actual threat situations were used.…”