Appunti di affective neurosciences and psychopatology, esame Prof. Buodo

What is affective neuroscience

The term affective neuroscience was coined in 1992 by Panksepp and it refers to a discipline that studies the neural mechanisms underlying the recognition, generation, experience, and regulation of emotion, essentially the neural basis of human emotion. Affective neuroscience aims to answer questions regarding which are the brain systems underlying emotional processing, if any emotion represents a function of a specific brain region or not, and about how emotion processing in the brain interacts with cognition, language, and motivation. Affective neuroscience tries to answer these questions through basic research with animal models. This is because the essential neural substrates for a multitude of emotional-affective processes are concentrated in those sub-cortical regions of the brain that we share homologously with other mammals. It also involves human studies, in the case of lesions of psychopathology but also in healthy individuals, and this through neuroimaging studies, with sMRI, fMRI, PET. In the case of animals, the studies focused on rodents, cats, nonhuman primates and are made through manipulation of brain structures to cause or alter the expression of emotion or with measures of neural activity correlated to naturally-induced emotion.

Historical context and theories

Previously to the emergence of this discipline, according to Damasio, the role of emotions in human and animal behavior was neglected by the cognitive revolution, because emotions were regarded as too subjective and could not be studied accurately. But then an affective revolution occurred, giving importance to the role of emotions, also unconsciously, in intelligent life. In The Emotional Brain (1996), LeDoux established the notion of the Low and the High roads to show, among other things, that emotional responses can occur without the involvement of cognitive processing systems of the brain. According to LeDoux (1996), when a certain region of the brain is damaged, animals or humans lose the capacity to appraise the emotional significance of certain stimuli without any loss in the capacity to perceive the same stimuli as objects.

Early theories of emotion

James, who published in 1884 the book What is an Emotion?, in his theory developed with Lange, believed that emotion is generated by awareness of the physiological changes that occur in response to stimuli in the environment. According to this theory, you run and then you are afraid; so you are afraid because you run. Anyway, visceral sensation cannot account exclusively for emotion: a central system for emotional experience is needed.

In the Cannon-Bard’s theory, based on studies of the effect of brain lesions on the emotional behavior in cats, the thalamus relays sensory information to the hypothalamus (visceral changes) and the cortex (emotional experience and top-down control). Years later, Olds and Milner demonstrated that the thalamus is also involved in the processing of reward. Cannon-Bard’s theory had the merit to include for the first time neural circuits involved in the expression of emotion, but it focused on responses to unpleasant stimuli and the amygdala was left out.

In 1937, Papez, with his circuit, proposed a mechanism of emotion in which sensory information follows two separate streams: thought and feeling. The cingulate cortex generates the conscious emotional experience through either stream and modulates emotional responses through top-down control. Then, MacLean integrated Papez’s and Cannon-Bard’s theory with findings obtained with bilateral removal of temporal lobes in monkeys. He viewed the brain as a triune architecture: reptilian brain, old mammalian brain, and neommalian brain. MacLean’s old mammalian brain (limbic system) included the anterior thalamic nuclei, the hippocampus, the hypothalamus, the septum, the amygdala, and cingulate cortex. The limbic system, and particularly the hippocampal formation (that included also amygdala), generates emotional feelings by integrating the perception of sensory input and feedback of bodily changes. Anyway, the concept of a unified limbic system is imprecise, also because regions that are conventionally placed into the limbic system are not unique for emotion.

The role of the amygdala

The amygdala is divided into different nuclei: lateral nucleus, basolateral, basal central and medial nuclei. The lateral nucleus receives sensory input from the thalamus and from the cortex; through the basolateral nucleus, it is connected with the central nucleus, which represents the site of the output to the hypothalamus and brainstem. There are three processes in which the amygdala plays a key role: the processing of social signals of emotion, emotional learning (fear conditioning), and the consolidation of emotional memories.

The amygdala activates in response to emotional facial expressions especially fear (Fitzgerald et al., 2006) and even when fearful eyes alone are presented subliminally (Whalen et al., 2004). It responds also when fear is conveyed by non-facial expressions, such as non-verbal vocal sounds or by whole-body movements that signal fear.

Fear conditioning consists of a neutral (conditioned) stimulus (CS), such as a tone, paired with an aversive unconditioned stimulus (US), such as a mild footshock. CS-US pairings result in an association of the CS and US, whereby the presentation of the CS alone subsequently elicits a conditioned fear response, such as freezing. The association occurs at the level of the lateral nucleus. Indeed, bilateral lesions of the lateral nucleus of the amygdala reduce the elevation of blood pressure and the duration of freezing evoked by the CS (LeDoux et al., 1990). Fear conditioning and unconditioned response to fear stimuli are mediated by two routes involving the amygdala: direct thalamo-amygdala route (enables instant fear response) and the thalamo-cortico-amygdala route (slower and complex analysis). Only lesions to both pathways impair fear conditioning. Both pathways most likely process emotional stimuli unconsciously, with conscious awareness of the stimulus requiring prefrontal areas.

The amygdala is selectively involved with the formation of enhanced long-term memory of emotionally arousing events. Indeed, activity of the right amygdala while viewing emotionally arousing films was highly correlated with the number of emotional films recalled three weeks later (Cahill et al., 1996). The amygdala is not itself a site of long-term explicit or declarative memory storage, but serves to influence memory-storage processes in other brain regions.

PFC

The prefrontal cortex (PFC) is involved in representing the emotional and motivational value of stimuli (both primary and secondary reinforcers), monitoring changes or reversals in the reward value of learned stimuli, using feedback signals from the body to guide complex decision-making, cognitive control through action selection, response inhibition, performance monitoring, emotion regulation, and social processing. The activation of the medial orbitofrontal cortex reflects the relative (not absolute) reward value of stimuli (context-dependent). Dorsolateral and orbitofrontal cortex activate upon changes in reward contingencies (affective switching).

Somatic markers (SM) are somatic responses (autonomic or muscular) that occur during emotionally-relevant situations and thus “mark” the value of the event and, most importantly, the value (“good” or “bad”) of the outcomes of a given course of action. SM develop through experience, as various bodily states become associated with positive and negative events. When one contemplates possible options before making a decision, somatic signals marking options as either positive or negative are re-activated, allowing to weigh options and ultimately make a choice. A key role in the neural system necessary for implementing advantageous decisions is played by the ventromedial PFC (vmPFC). The vmPFC integrates and regulates the neural representations of actual or predicted somatic states associated with options, and uses them to guide decision-making based on the value a current event has had in the past. This “emotion-guided decision making” is crucial in conditions of complexity and uncertainty, where detailed analysis of options based on costs and benefits would be overly time-consuming or even impossible. vmPFC patients fail to activate a negative marker for the bad decks based on past punishment history, and thus are insensitive to the possibility of further punishment on those decks (myopia for the future).

According to the Davidson’s valence asymmetry hypothesis, two basic emotional/motivational systems exist:

• The approach system, moving toward a desired goal, facilitates appetitive behavior and generates positive effect with involvement of left PFC.
• The withdrawal system generates negative effect with involvement of right PFC.

Damage to the left PFC is associated with increased likelihood of developing depressive symptoms. The effect of different emotion regulation strategies can be understood in terms of the stages of the emotion generation sequence that they influence. The emotion-modulatory effects of reappraisal stem from interactions between cognitive control processes implemented in prefrontal and cingulate regions and emotional appraisal processes implemented in multiple emotion-related structures, including the amygdala. Up-regulation uniquely activates the left anterior medial PFC, retrieval of emotion knowledge, and emotion labels that can be used to describe an event in increasingly negative terms. Down-regulation uniquely activates right lateral PFC, response inhibition, and right orbitofrontal PFC, changing context-sensitive motivational relevance.

The mPFC is engaged in inferring enduring psychological characteristics of others and the self, or interpersonal norms and scripts, and, to a lesser extent, temporary states (e.g., intentions, goals, desires). The mPFC integrates social information across time and allows reflection and representation of traits and norms at a more abstract cognitive level. Trait information about unfamiliar others selectively engages the dorsal part of the mPFC, whereas making trait inferences about familiar others or the self implicates the ventral part (close proximity of the reward system in the orbitofrontal cortex?).

ACC

The anterior cingulate cortex (ACC) is involved in integration of visceral, attentional and emotional information; generation of subjective feelings, i.e., conscious emotion experience (connections with insula); emotion regulation (connections with PFC); representation of autonomic arousal and generation of autonomic changes (connections with PFC); monitoring of conflict between the current functional state of the organism and any new information with potential affective consequences; pain anticipation and analgesia, pain control, social pain. Significant correlations between activity in dorsal ACC and different measures of autonomic arousal during cognitive (mental arithmetic), motor (physical exercise), and emotional tasks. Affective and sensory components of pain are encoded in different regions of the cingulate cortex (pACC and PCC, respectively). The pain of social rejection: activity in the pACC is increased during social exclusion, and correlates with the level of experienced distress. So the experience of social and physical pain share a common neuroanatomical basis. The dorsal ACC is more sensitive to conflict in the cognitive domain, whereas the rostral ACC is more activated in response to emotional interference.

Insula

The insula is involved in representation of bodily changes (connections with ACC); empathy (connections with ACC); decision-making in complex situations (somatic marker) (connections with PFC and ACC); disgust processing. The insula is more activated when seeing another feeling pain. Observing one person being excluded (vs. included) by others activates regions associated with mentalizing (dmPFC, mPFC), meaning that simply watching someone experiencing social pain may not automatically elicit distress like observing physical pain. Highly empathic individuals activate both mentalizing regions and pain-related regions (dorsal ACC, anterior insula), meaning that understanding the situation and imagining the victim's affective responses might only elicit pain-related neural activity.