Appunti di affective neurosciences and psychopatology, esame Prof. Buodo

PERIAQUEDUCTAL GRAY

The PAG is involved in: behavioral expression of survival-related, defensive responses during threat and stress (flight/fight/freezing behavior); modulation of the expression of predatory behavior; modulation of nociceptive sensory information and analgesia (connections with ACC). The PAG is organized into columnar subregions with distinct ascending and descending connections, that coordinate different survival-related responses during threat and stress. vPAG lesion diminishes freezing, indicating that the ventral PAG is necessary for defensive freezing behavior. dlPAG lesion enhances freezing, indicating that the dorsolateral PAG exerts tonic inhibition over the ventral PAG. Activation of the human PAG is linked to a parasympathetically dominated autonomic response that is characteristic of freezing behavior in both animals and humans - passive defense mode that subserves a state of attentive immobility.

When threat is detected ("cue phase"): activity in the PAG

and rACC is greater for the predator cue than for the neutral cue. The “imminence effect” in the predator condition (“chase phase”) for distal threat, activity is greater in vmPFC (different alternative goal-directed behaviors are compared in order to choose the most effective strategy to avoid the threat or distress); for proximal threat, activity is greater in the PAG (fast and obligatory response is required, preparing the organism for survival and possible tissue damage).

WHAT IS FEAR

LeDoux defined fear as the behavioural adaptation that allows organisms to detect and respond to danger. An important distinction is made between innate, or unconditioned fear responses and learned fear, elicited by neutral stimuli associated with innate threats. In the fear system amygdala is a central node. The emotional stimulus, from the sensory thalamus reaches the amygdala through a low road, a direct connection, and through a high road, passing through the sensory cortex. As showed

by Romanski and LeDoux,1992 deconstruction of neither pathways (thalamo-amygdala projections and thalamo-cortico-amygdala pathway) alone interferes with fear conditioning, but combined lesions of the two pathways do. So neither pathway is necessary, each is sufficient. Both pathways process emotional stimuli unconsciously. Consciousness is related to working memory, the dlPFC, ACC and OFC. The systems providing inputs to WM include immediately present stimuli triggering, long-term explicit memories, and amygdala activation. This may be the stuff that fearful feelings are made of. According to the LeDoux model referring to the role of amygdala in human fear activation, (1) fear stimuli should activate the amygdala. Amygdala activation should be rapid and not require conscious recognition of the eliciting stimulus. When exposure and masking times only allowed for incomplete visual processing in V1, the amygdala responded to both types of stimuli, so the amygdala responds to anything that might turn.

out to have important consequences for safety and for survival. Activation of the amygdala should be independent of focal attention to the eliciting stimulus. Activation of the amygdala should not require cortical activation. Indeed, in G.Y., a patient with hemianopia, that denied any perception of faces presented in his blind hemifield, blind hemifield presentation of fearful faces evoked increased responses of the bilateral amygdala (Morris et al., 2001). The residual ability might depend on the colliculo-thalamo-amygdala neural pathway, that can process fear-related stimuli independently of both the striate cortex and visual awareness. The amygdala should be directly activated by visual stimuli via a subcortical route that includes the superior colliculus of the midbrain and the pulvinar nucleus of the dorsal thalamus. Such signals from amygdala then may initiate the fight/flight mechanisms of the brainstem, including the locus coeruleus from which noradrenergic pathways are triggered to provide.

rapidly and diffusely excitatory innervation of the cortex, that facilitates an increase in alertness.

S.M. is a patient with Urban-Wiethe disease, characterized by a bilateral amygdala damage, with impaired fear conditioning and fear recognition in facial expressions. She was able to identify which situations are supposed to evoke fear, she can recognize fear from body cues and from prosody of someone's voice. But, she shows a lack of subjective fear experience and behavioral signs of fear. She recalls several autobiographical events when she felt afraid, all occurring before age 10. Amygdala degeneration due to calcifications develops progressively, usually beginning in childhood. S.M. case suggests a central role of amygdala in triggering a state of fear. While non fear-related emotions are likely triggered by brain sites that project to the hypothalamus and the brainstem without an intermediate link in the amygdala. Anyway, a study by Feinstein et al., 2013 shows that amygdala is

nonnecessary in internally-triggered fear. Patients with bilateral amygdala damage experienced fear and also panic attacks after the inhalation of CO2, this because CO2 may directly activate extra-amygdalar brain structures underlying fear and panic.

Learned fear can be modify in three ways:

Extinction: a process by which learned fear responses are no longer expressed after repeated exposure to the conditioned stimulus with no aversive consequences. Activity in the amygdala increases during fear conditioning and decreases during extinction. By contrast, activity in the vmPFC decreases during fear acquisition and increases during extinction, so it represents a top-down inhibitory control over fear responses to prevent emotional perseveration.

Reversal: a procedure in which fear responses are switched between two stimuli following a reversal of reinforcement contingencies. The amygdala and the striatum increased responses to the conditioned stimulus associated with the unconditioned stimulus.

During acquisition and also to the new CS after reversal. While vmPFC responses are stronger to the new CS- vs CS-. The vmPFC might encode which stimuli are safe.

Regulation: a set of processes involving the use of strategies aimed at attenuating a conditioned fear response. For the regulation of amygdala activity, both dlPFC and vmPFC are critical.

Changing learned fear relies on a common neural network. The intra-connectivity between the vmPFC, the amygdala and the striatum would subserve different functions: inhibitory control over fear responses via vmPFC-amygdala connections; output to motor systems via amygdala-striatum connections to initiate instrumental responses to actively cope with conditioned fear.

THE NEURAL BASIS OF REWARD

Reward is not a sensation or something desired for its pleasant qualities. It lies in a set of active processes of the brain and mind in response to a stimulus, rather than the stimulus itself. Reward can be parsed into specific psychological components: wanting,

The motivational component, attribution of incentivesalience to a percept or representation; learning, allow cues to raiseexpectations of future reward, and to guide goal-directed behavior; liking, theaffective quality of experience, pleasure, or hedonic impact of reward. Eachprocess includes both explicit and implicit components. Wanting (cognitiveincentives and incentive salience); learning (cognitive and associative); liking(conscious opleasure and core hedonic impact).

Olds and Milner demonstrated though electrical stimulation in laterlhypothalamus, medial forebrain bundle (from VTA and nucleus accumbensthough lateral hypothalamus) and septal area (set of nuclei below the anteriorpart of the corpus callosum) that there is an anatomically identifiable rewardcircuit. The meso-cortico-limbic circuit includes a meso-limbic pathway(dopaminergic neurons in the VTA project to the striatum) and a meso-corticalpathway (dopaminergic projections from the VTA to the dorsal and ventral PFC,OFC, ACC).

In rats, different neural populations in the ventral pallidum exhibit different firing profiles for prediction (learning) and incentive salience (wanting). Learning and wanting may involve separate coding in humans too. Wanting is mediated largely by midbrain dopamine projections to the NAcc. The "liking" system comprises a collection of interactive hedonic hotspots embedded in the nucleus accumbens and ventral pallidum (but note that some uniquely human abstract pleasures have cognitive qualities too, that depend on cortical areas, such as OFC, ACC, insula). Hotspots in NAcc and Ventral Pallidum act as a functional unit for mediating pleasure enhancements. The hedonic hotspot located in the ventral pallidum may be especially crucial to the normal capacity for pleasure. The ventral pallidal hotspot is the only known site in the brain where a small lesion eliminates normal pleasure. Indeed, patients with selective bilateral lesions of the globus pallidus show severe anhedonia. Moreover,

Stimulation of the glob pallis alleviates depressive symptoms. Some pieces of evidence demonstrates that a dissociation exist between wanting and liking process. In rats, the manipulation of dopamine systems changes wanting-related motivated behaviour without affecting liking. Moreover, oral administration of d-amphetamine induces an increase in extracellular dopamine in bilateral NAcc correlates significantly with self-reported "Want Drug", but not with self-reported "Like Drug" and mood elevation, so wanting is enhanced but liking is not affected. The "dissociation" of "wanting" and "liking" might explain "irrational desires" that could underlie reward-related psychopathologies.

In human neocortex, pleasure appears most faithfully represented by activity in orbitofrontal cortex, particularly in a mid-anterior subregion. The mid-anterior OFC most reliably represents sensory pleasures (tastes) and may also encode pleasures.

of sexual orgasm, drugs, and music. The ability to process primary rewards may occur phylogenetically and ontogenetically earlier than the ability to process secondary rewards, which represent more evolved adaptive behavior. A functional organization along a postero-anterior axis has also been shown in the OFC, with more complex or abstract reinforcers (such as monetary gain) being represented more anteriorly, and less complex reinforcers (such as taste, or sex) more posteriorly. Anyway, the human cortex is not needed to cause pleasure, as in the case of a man without OFC, insula and ventral ACC had manifestations of pleasure.

In a recent study by Castro and Berridge (2017) hedonic hotspots were found in anterior orbitofrontal cortex and in posterior insula in the rat's brain.

NEURAL BASES OF AGRESSION

Moyer defines aggression as a behaviour that causes or leads to harm, damage or destruction of another organism.