Studies of fear conditioning (see Figure 1a) have provided a map of the neural circuitry that implicates the amygdala as a key structure in the mediation of fear (see Figure 1b). Located at the anterior medial portion of each temporal lobe, the amygdala is composed of about a dozen different nuclei, each with a distinctive set of connections. Lesions of the entire amygdala seem to abolish fear in monkeys with Klüver-Bucy syndrome. Lesioning just the central nucleus of the amygdala has the same effect, preventing blood pressure increases and freezing behavior in response to a conditioned fear stimulus.

Figure 1  The Circuitry of Fear
a) In one classical-conditioning procedure to study fear, a tone is associated with a mild electric shock, which causes increased blood pressure and “freezing” (left and middle); eventually the tone alone elicits these responses (right). (b) Proposed circuitry for the mediation of conditioned fear responses. (c) A fear-inducing stimulus reaches the thalamus and is relayed either directly to the lateral nucleus of the amygdala (the “low road” for unconscious reactions to threat) or via the cortex and hippocampus (the “high road,” involving more detailed and conscious processing of stimuli). The information ultimately reaches the amygdala’s central nucleus, which projects to three different brain nuclei (central gray, lateral hypothalamus, and bed nucleus of stria terminalis), each of which seems to produce a different component of the fear response. (After LeDoux, 1994, 1996.)

On its way to the amygdala, via various sensory channels, information about fear-provoking stimuli reaches a fork in the road at the level of the thalamus (the thalamus acts like a switchboard, directing sensory information to specific brain regions). A direct projection from the thalamus to the amygdala, nicknamed the “low road” for fear responses, bypasses conscious processing and allows for immediate reactions to fearful stimuli (LeDoux, 1996). An alternate “high road,” pathway routes the incoming information through sensory cortex, allowing for processing that, while slower, is conscious, fine-grained, and integrated with higher-level cognitive processes, such as memory (see Figure 1c).

Contributions from prefrontal cortex and the anterior cingulate offer an additional level of fear conditioning: observational fear learning, in which fear of potentially harmful stimuli is learned through social transmission (Olsson and Phelps, 2007). So, to extend our example, an individual can learn to fear scorpions by observing signs of fear and pain in others, without personally experiencing a scorpion attack. Given the considerable adaptive benefits that it confers, it’s not surprising that observational fear learning is seen in species as diverse as mice, cats, cows, and primates, including humans.

Interconnections within the amygdala also form an important part of the story, as Figure 1c illustrates. Information about the stimulus (the sound in Figure 1a) from several brain regions, including sensory cortex, reaches the lateral portion of the amygdala first; and evidence suggests that neurons here encode the association between specific stimuli and aversive events like electric shock (Maren and Quirk, 2004). The lateral amygdala triggers a network within the amygdala, ultimately activating the central nucleus. The central nucleus then transmits information to various brainstem centers to evoke three different aspects of emotional responses (see Figure 1c): pathways through the central gray (also called periaqueductal gray) evoke emotional behaviors, those through the lateral hypothalamus evoke autonomic responses, and those through the bed nucleus of stria terminalis evoke hormonal responses.

Learned fears are notoriously slow to extinguish; in our example (see Figure 1a), once the shock and the sound have been paired, the auditory tone must be presented without shock many times before animals stop freezing in response. Mice missing one of the two types of cannabinoid receptors (see Chapter 4) have an even harder time unlearning their fearful reaction to a tone (Marsicano et al., 2002), suggesting that stimulation of these receptors normally extinguishes learned fears. If so, then it may be possible to develop cannabinoid drugs to treat phobias in humans.

Disgust has been studied only in humans, where functional MRI suggests that a cortical region called the insula and the nearby putamen (part of the basal ganglia; see textbook Figure 2.14a), but not the amygdala, are activated when we see or hear someone expressing disgust (Phillips et al., 1998). Confirming this idea is the report of a man whose head injury damaged these two regions: he was very poor at recognizing disgust in other people but was normal in recognizing other emotions (Calder et al., 2000).

The feeling of mirth leading to laughter has also been studied only in humans so far (but note that Panksepp [2007] argues that rats also laugh). People with stroke damage to the right frontal lobe often stop finding anything funny (Shammi and Stuss, 1999), suggesting a cerebral asymmetry in humor. But fMRI studies of people exposed to different kinds of humor suggest that the prefrontal cortex of both hemispheres is active when we experience mirth (Goel and Dolan, 2001). Electrical stimulation of the prefrontal cortex also lifts mood, even in people with depression who have not responded to other treatments (Mayberg et al., 2005). So there’s good evidence that the prefrontal cortex, either on the right or bilaterally, is activated when we laugh.

Considerable progress has been made in identifying the neural circuits of other emotions in addition to fear (Panksepp, 1998, 2000). Figure 2 presents an overview of some of this information. Note that, in general, there is no one-to-one correspondence between an emotion and a brain region; that is, each emotion involves activity of more than one brain region, and some brain regions are involved in more than one emotion.

Figure 2  Rodent Brain Regions Involved in Some Basic Emotions
(After Panksepp, 2000.)


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