[HD 202] E01-T04-Neuroscience of Emotions - Limbic System

• The limbic lobe is a set of surface medial structures forming a border (or limbus) around the brain stem.
• Limbic lobe includes the parahippocampal gyrus and cingulate gyrus
• The Limbic System is a neural system for mediating emotion
• There is no single system mediating emotion, but the limbic system provides a useful principle for understanding emotional behavior and higher-level neural functions.

Papez Circuit

• The Papez Circuit is an emotion circuit.
• It is a circuit interconnecting cortical areas with thalamic and hypothalamic structures to control the visceral brain.
• The limbic loop route: hippocampus, mammillary bodies, anterior nucleus of thalamus, cingulate gyrus, parahippocampal gyrus, and back to the hippocampus. Fornix projections go from the hippocampus down to the mammillary bodies in the hypothalamus. Mammillary bodies project to the anterior nucleus of the thalamus, which projects to the cingulate cortex.
• The cingulate cortex then projects back to the parahippocampal gyrus and hippocamus
• Hippocampus is the heart of the Papez circuit.
• The Amygdala is not in the Papez circuit, even though it is heavily involved in emotion.
• The limbic system is a set of medial areas interspersed between sensory-motor areas and the hypothalamus.
• No direct connection from hypothalamus to sensory-motor areas is shown
• Information has to go through the limbic system

Parts of the Limbic System

• Consists of telencephalon, diencephalon, and midbrain structures.
• Telencephalon components: orbitofrontal cortex, cingulate gyrus, nucleus accumbens, hippocampus, fornix, parahippocampal gyrus (PHG), and amygdala.
• Diencephalon components: anterior nucleus and medial dorsal nucleus of the thalamus, and the mammillary bodies of the hypothalamus.
• Midbrain components: ventral-tegmental area (VTA), dorsal raphe nucleus, and interpeduncular nucleus.
• The internal capsule contains axons of neurons in the cortex that descend.
• The Nucleus accumbens (ventral striatum) is where the caudate nucleus and putamen meet
• Amygdala is not part of the cortex, but a subcortical structure in the temporal lobe while the hypothalamus is on the walls of the third ventricle.
• Mammillary bodies project up to the anterior nucleus of the thalamus via the mammillothalamic tract

Function of the Limbic System

• A set of medial areas between sensory-motor areas (stimuli) and the hypothalamus (drives) which connects them to your drives.
• It selects the appropriate target/object for drives such as the amygdala identifying an appropriate object and the hippocampus identifying the appropriate context through spatial and memory functions.

Amygdala functions

• Assigns affective (emotional) significance to sensory stimuli and to initiate appropriate emotional responses
• There is a direct connection to emotion-generating structures
• Amygdala also projects to the stria terminalis up to the thalamus and hypothalamus, as well as through the periaqueductal gray in the midbrain.
• Projects to the midbrain through the periaqueductal gray, where fear responses are generated (freezing, startle responses, increasing heart rate, etc.)

Kluver-Bucy Syndrome

• Rare neuropsychiatric disorder due to lesions affecting bilateral temporal lobes, especially the hippocampus and amygdala.
• Characterized by: hyperorality, hypermetamorphosis, hypersexuality, bulimia, placidity, visual agnosia, amnesia
• Bilateral removal of the amygdala and inferior temporal cortex (in monkeys) results in tameness, loss of fear to predators, attempting to eat non-food objects, and attempting to copulate with other species
• Sexual drives are still intact but they are misdirected

Fear and the Amygdala

• Best studied with an emotion that has readily observed physical effects in mammalian animals
• Fear can be easily detected and manifests as freezing in rats, skin conductance response in humans, etc.

Pavlovian Conditioning

• Association of a conditioned stimulus and an unconditioned stimulus transfers the instinctual response to the conditioned stimulus.
• The learning to salivate in response to the sound of a bell is one example
• The conditioned stimulus is the Bell
• The unconditioned stimulus is the Meat
• The conditioned response is Salivation
• Has three steps: Habituation, Conditioning, Extinction
• Habituation: decreases response to CS alone, before any conditioning
• Conditioning: pairing of CS with US. The organism now responds to CS with CR, which is the same response that US triggers but with a different stimulus.
• Extinction: CR starts to disappear after CS is delivered a number of times without US
• The organism always remains susceptible to the same patterns
• Before Conditioning: the unconditioned stimulus generates an unconditioned response. The response is natural and does not require any training
• During Conditioning: associating condition stimulus with the unconditioned occurs should occur before or during the same time as unconditioned stimulus

After Conditioning

• Conditioned stimulus creates a new conditioned response.
• Classical fear conditioning requires the amygdala
• Pavlovian conditioning in rats involved a tone as the conditioned stimulus and a shock as the unconditioned stimulus , with freezing exhibited as the conditioned response

Output Responses

• Central nucleus makes the hypothalamic response (autonomic-sympathetic), periaqueductal gray (freezing), and reticular formation (startling)
• The fear response pathway can still occur even if the cortex is damaged
• Medial prefrontal cortex controls the amygdala, determining when fear response is appropriate.
• Fear memory lasts forever, but the medial prefrontal cortex determines when they are expressed.

Pavlovian conditioning in animals

• In fear conditioning experiments have been observed in various animal groups and been found to be relatively permanent
• Changes in behavior can be implemented by controlling the fearful response rather than the memory itself
• Reptiles, bird, and mammals use the amygdala to express fear conditioning

Role in Amygdala in Pavlovian Conditioning

• Amygdala lesions prevent fear conditioning because the amygdala is responsible for storing the tone-shock association
• Emotional memory is stored for a lifetime, hence trauma is stored for a lifetime and cannot be forgotten

Neurophysiology of the Amygdala

• Requires the neurons of the amygdala to fire after conditioning in response to CS
• Neurons don't respond to the to CS stimulus before conditioning
• Rat’s amygdala has 3 general parts: basolateral, lateral and central nucleus
• Lateral nucleus receives signals from Auditory Cortex and Medial Geniculate Cortex

Pharmacologic Inactivation of Prelimbic & Infralimbic Areas

• Pharmacologic inactivation of PL & IL have opposite effects on freezing
• Prelimbic area ("GAS") is necessary for fear expression and freezing response so implications of inactivation causes decreased fear expression and reduced freezing response and facilitates extinction
• Infralimbic area ("BRAKE") is necessary for fear extinction, so implications of inactivation results in increased fear expression and impaired extinction

Translating rodent findings to humans

• Homologues PL and IL on human and rodent brains,
• Human amygdala (AMY), Hippocampus (HIPP), Infralimbic Cortex (IL), Prelimbic Cortex (PL), Dorsal Anterior Cingulate Cortex (dACC), Ventromedial Prefrontal Cortex (vmPFC)

Fear Conditioning in Human Subjects

• Electrode on subject's wrist with Yellow square not providing anything and the Blue square providing a minor shock.
• The square becomes associated with shock that measured with skin conductance response
• Implications for people with PTSD is they can extinguish fear but eventually comes back
• Imbalance in Prelimbic & Infralimbic activation is when there is dACC activity with limited vmPFC activity
• dACC/vmPFC ratio can be used as a biomarker for susceptibility to anxiety disorders

Case of S.M.: Urbach-Wiethe disease

• Loss of amygdala, but retained declarative memory (hippocampus intact) and lost emotional memory
• Could not learn square association with fear

Damage impairs Emotional Recognition

• There is something in human amygdala to derive fear from the face
• Normal people look at the eyes
• Patient S.M. tends to avoid looking at them or recognize eyes and fear
• Patients with autism might not be able to see the face signals

Brain Activity

• When the abnormal face is shown versus a normal face
• The higher-order visual cortex (face area) in the occipital lobe is responsible for recognizing faces versus when higher activity with visual recognition

Other Functions of Amygdala

• Amygdala controls condition test aversion which is to avoid foods for cancer patients who experience nausea

Electrical Stimulation of the Amygdala

• It produces feelings of fear and anxiety, autonomic arousal and pituitary activity, and production of seizure or déjà vu

Development of the Fear Circuit

• The fear circuit is made up of the amygdala, hippocampus, and the prefrontal cortex.
• Fear handled: Amygdala (infancy to adolescence) handles fear association with stimuli (sensitive age between 0-2 and 9-11), Hippocampus (childhood to adulthood) handles conscious memories and context, Prefrontal Cortex (later childhood to adulthood) handles regulation of amygdala and handles modulation of fear through the extinction and anticipation of the consequences of action
• During childhood/adolescence: Early deprivation can increase risks, the material buffering and social support reduces the development timing