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Scientists from Wellcome Trust claim to have identified for the first time what happens in our brain in the face of an approaching fear. They measured activity in the brain using fMRI while a subject played a game similar to Pac-Man and received an electric-shocks when they were caught by the video game predator.

They found that activity in the ventromedial prefrontal cortex (behind the eyebrows) increased when the enemy was in the distance - this part of the brain is active when one is planning how to respond to a threat. As the video game enemy approached, predominant activity shifted to the periaqueductal grey - the part of the brain responsible for flight or fight and preparing for reaction to pain.

The title of their study is 'Free Will Takes Flight', as it shows that we act more on impulse when a threat increases.

Abstract can be found here

Article in Science Magazine can be found here

From Science 24 August 2007: Vol. 317. no. 5841, pp. 1043 - 1044

Neuroscience: The Threatened Brain

Stephen Maren

The world is a dangerous place. Every day we face a variety of threats, from careening automobiles to stock market downturns. Arguably, one of the most important functions of the brain and nervous system is to evaluate threats in the environment and then coordinate appropriate behavioral responses to avoid or mitigate harm.

Imminent threats and remote threats produce different behavioral responses, and many animal studies suggest that the brain systems that organize defensive behaviors differ accordingly (1). On page 1079 of this issue, Mobbs and colleagues make an important advance by showing that different neural circuits in the human brain are engaged by distal and proximal threats, and that activation of these brain areas correlates with the subjective experience of fear elicited by the threat (2). By pinpointing these specific brain circuits, we may gain a better understanding of the neural mechanisms underlying pathological fear, such as chronic anxiety and panic disorders.

To assess responses to threat in humans, Mobbs and colleagues developed a computerized virtual maze in which subjects are chased and potentially captured by an "intelligent" predator. During the task, which was conducted during high-resolution functional magnetic resonance imaging (fMRI) of cerebral blood flow (which reflects neuronal activity), subjects manipulated a keyboard in an attempt to evade the predator. Although the virtual predator appeared quite innocuous (it was a small red circle), it could cause pain (low- or high-intensity electric shock to the hand) if escape was unsuccessful. Brain activation in response to the predatory threat was assessed relative to yoked trials in which subjects mimicked the trajectories of former chases, but without a predator or the threat of an electric shock. Before each trial, subjects were warned of the contingency (low, high, or no shock). Hence, neural responses evoked by the anticipation of pain could be assessed at various levels of threat imminence not only before the chase, but also during the chase when the predator was either distant from or close to the subject.

How does brain activity vary as a function of the proximity of a virtual predator and the severity of pain it inflicts? When subjects were warned that the chase was set to commence, blood oxygenation level-dependent (BOLD) responses (as determined by fMRI) increased in frontal cortical regions, including the anterior cingulate cortex, orbitofrontal cortex, and ventromedial prefrontal cortex. This may reflect threat detection and subsequent action planning to navigate the forthcoming chase. Once the chase commenced (independent of high- or low-shock trials), BOLD signals increased in the cerebellum and periaqueductal gray. Activation of the latter region is notable, as it is implicated in organizing defensive responses in animals to natural and artificial predators (3, 4). Surprisingly, this phase of the session was associated with decreased activity in the amygdala and ventromedial prefrontal cortex. The decrease in amygdala activity is not expected, insofar as cues that predict threat and unpredictable threats activate the amygdala (5, 6).

However, activity in these brain regions varied considerably according to the proximity of the virtual predator and the shock magnitude associated with the predator on a given trial (see the figure). When the predator was remote, blood flow increased in the ventromedial prefrontal cortex and lateral amygdala. This effect was more robust when the predator predicted a mild shock. In contrast, close proximity of a predator shifted the BOLD signal from these areas to the central amygdala and periaqueductal gray, and this was most pronounced when the predator predicted an intense shock. Hence, the prefrontal cortex and lateral amygdala were strongly activated when the level of threat was low, and this activation shifted to the central amygdala and periaqueductal gray when the threat level was high.

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