7 Limbic Dropbox.docx

7: Limbic System The limbic system consists of: 1. 2. 3. 4.

Amygdala Hypothalamus Hippocampus Association Cortices

There are several other guys outside the traditional limbic system that still play limbic roles: 1. 2. 3.

Reticular Activating System Periaqueductal Grey Nucleus Accumbens

Amygdala: The amygdala is important in learning and emotion. As mentioned (and joked about with Rae) damage to the amygdala results in Kluver-Bucy Syndrome: which comes with a bunch of nasty symptoms including impaired threat assessment. The amygdala found in the medial temporal lobe, is important in conditioned emotional responses. The amygdala receives specific stimuli; be it auditory, visual, olfactory, etc, and it “tags” that stimuli it with memory and an emotion. In the future, that same stimuli can trigger that memory and emotion: The amygdala is always externally focused, and processing sensory information to tell if there should be an emotional response with it. -

Examples:

1.

When there is a sound; you are zapped with electricity. Your amygdala connects the auditory stimulus (sound) with an emotion (fear) because that sound is associated with something painful. In the future, when there is that tone (stimuli) it will trigger the same emotion (fear) which will cause a response.

2.

A smell is able to trigger a whole cascade of feelings. It can be good feelings, such as when you’re walking in fall and smell fall and think about nice holiday things The amygdala has tagged emotionally charged experiences, and tagged those memories with a specific emotion.

3.

When you touch a hot stove, your amygdala tags the memory of and sensation with fear, so you know not to touch hot stoves in the future.

The Central Nucleus of the Amygdala is the structure involved in tagging emotional information: sad things, happy things, scary things. Since the amygdala and the hippocampus are connected to each other, it makes it easy for the amygdala to tag memories with specific emotions. -

The amygdala is not storing information; rather, it’s tagging information.

Let’s say you see a clown: 1.

2.

Visual information is picked up, and the clown is registered through the basolateral nucleus of the amygdala: the “door” to the amygdala, and is receiving information from the Cerebral Cortex That signal is sent to the Central Nucleus: which is the main processor of that visual stimuli. It will then activate appropriate responses to that fearful stimuli: a. Hypothalamus: hypothalamus is the output center of the limbic system. Hypothalamus is going to cause release of appropriate hormones in response: i. Scary Stimulus: It could be CRH  Anterior Pituitary  ACTH  Cortex  Cortisol  Medulla  Norepinephrine: primes the body to move. Hypothalamus can also directly stimulate Locus Ceruleus. ii. Happy Stimulus: release dopamine and make you happy :D

b.

c.

Cortex: this is trigger higher thought processes, planning, and thinking: this is how you will consciously respond to the threat. You will plan on hiding, running away, locking a door, etc. Your body has been primed to move because of the norepinephrine: you move quickly. Periaqueductal Gray: This helps to modulate the behavioral reaction.

Hypothalamus: this is the effector of the amygdala. This mobilizes the body to react to stimuli 1.

2. 3.

Primitive Emotions: things like hunger, thirst, sex, rage, pleasure. Unlike the amygdala, these do not require a stimulus, and these can be quickly turned on and off. Internal Homeostasis: things like temperature, carotid blood chemistry, CSF, and circadian rhythm, and endocrine control. Controls the internal environment by: a. ANS output: hypothalamus can directly activate locus Ceruleus (second way to dump norepinephrine into system) b. Endocrine System: via the Hypothalamus-Pituitary-Adrenal Axis

Again, the Hypothalamus has several ways of controlling hormones. Back to scary response: 1. 2.

CRH  Anterior Pituitary  ACTH  Cortex  Cortisol  Medulla  Norepinephrine: primes the body to move. Hypothalamus directly activates the Locus Ceruleus to release Norepinephrine.

This system is very efficient if there is an actual threat, but if not, you can’t really “undo” the dumping of catecholamines in the blood. If the amygdala is improperly activated, then there will be this mechanism constantly; that’s called PTSD. There is a difference between peripheral and central responses to stress, and they interact with each other. Peripheral stresses, such as hyperthyroidism and hypertension can trigger this system in reverse. Anxiety peripherally, by things like elevated HR, Breathing Rate, etc. goes to the hypothalamus.

Hippocampus The hippocampus helps you store memory, but memory itself is sent to the temporal lobe where it is stored. 1. 2.

Amygdala tags a stimuli and event with an emotion. That goes to the hippocampus which sends information to the temporal lobe where it will be stored (papez circuit? Converting short term to long term memory).

Damage to the Hippocampus leads to deficiencies in: 1.

2.

Declarative Memory (facts): since the hippocampus is involved in the conversion and storage of memory, damage to the hippocampus (Alzheimer’s) will lead to a difficulty forming new memories. Old memories before the onset of Alzheimer’s will be unaffected, but there is a very difficult time remembering new things. Spatial Memory: the hippocampus is like the internal GPS system of the brain.

Parts of the Hippocampus: 1. 2.

3.

Dentate gyrus: cortex surrounding the hippocampus that serves to help store memory Parahippocampal gyrus: this is associated with memory retrieval and recognition of visual stimulation (scenes). Entorhinal Complex: pathway in and out of the hippocampal formation and this is associated with spatial memory.

Cortical Areas  Hippocampus  Back to the Cortical Areas: for processing.

Integration of Sensory Input: 1. 2. 3.

Cerebral Cortex: this is your higher thought functions, and has to do with analysis, planning, and restraint Limbic Structures: assessment of emotional importance, and this is involved in initiation of an emotional response. Emotion Based Outputs: a. Periaqueductal Gray b. Hypothalamus: activates ANS and endocrine systems c. Ventral Striatum: activates the motor systems.

With an anxiety disorder; this is all fired for no reason, or it activates for a good reason and never shuts down. When assessing an anxiety disorder, it may be helpful to distinguish cortical anxiety from peripheral anxiety: -

Cortical Anxiety: this manifests as scary thoughts, rapid thinking, mind pacing, etc. Peripheral Anxiety: these are things like tachycardia, tremors, sweating, etc.

Depending on which symptoms are most dominant, that can help guide treatment. To make things complicated, peripheral anxiety and cortical anxiety can activate and modulate each other.

Association Cortices: these are other parts of the limbic system: 1. 2.

Dorsolateral Prefrontal Cortex: this is working memory, executive function, and integration of many areas. Limbic Cortices: a. Orbitofrontal Cortex: this region of the brain is important with decision making, mood, restraint, and impulsitivity: i. It is often the first area of the brain affected with alcohol. ii. It is directly behind the eyes, so if someone is hit the head repeatedly, (boxing, etc.) they can damage this area and have difficulty with mood, restraint, and impulses. b. Cingulate: the cingulate is essential for motivation and emotional attachment to other people. This will also facilitate empathy, affection, concern, and proper emotional responses. If someone has autism, this area of the brain could be affected, and there might be no emotional difference between a family member and a rock. c. Temporal Cortex: while this is technically cortex and not limbic system, the temporal cortex is where memories are stored, and information here interacts with the emotions of the limbic system. i. Left: is verbal memory ii. Right: Spatial memory 5

Reticular Activating System: this is the part of the brain that “wakes up” the cortex, and maintains vitals and arousal. It has several important nuclei: -

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Locus Ceruleus: makes norepinephrine Raphe Nucleus: makes 5-HT (serotonin) o If someone doesn’t have enough serotonin release or serotonin receptors, they may become depressed.  SSRI: serotonin selective reuptake inhibitor: this allows serotonin to stay in the synapse longer, and this is also effective in treating anxiety by inhibiting the amount of norepinephrine released. SSRI’s directly inhibit Nor/Epi Release Ventral Tegmental Nucleus: this is associated with reward system: it secretes Dopamine and makes you happy. It also gives you something to look forward to o If someone has drug addictions, this area will be overstimulated, and the person will do ANYTHING it takes to build up more dopamine, because normal things in life don’t make them happy anymore. This is the mechanism behind addiction.

Periaqueductal Gray: this is a gray area that surrounds the cerebral aqueduct between the 3 rd and 4th ventricle. It works to modify emotional output, and it is involved in pain (oxy receptors?), sex, rage, and fear. -

When the dorsal lateral periaqueductal gray area was stimulated in rats, it provoked defensive responses: including freezing immobility, running, jumping, tachycardia, increased blood pressure and muscle tone. Stimulation of Caudal ventral lateral PAG caused immobile, relaxed posturing.

Basal Ganglia: while we certainly think about the basal ganglia being involved in movements, it also has some structures related to mood. -

Orbital Frontal Cortex and the Cingulate Gyrus  Ventral Striatum (Nucleus Accumbens)  Globus Palladus  Thalamus  OFC/Cingulate Gyrus.

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Nucleus Accumbens: this is found in the head of the caudate nucleus, and the main neurotransmitter to affect this area is dopamine. o o

Dopamine is required for happiness and looking forward to things. If someone does drugs for years, they damage the dopamine receptors and nothing will ever make them happy. Nucleus Accumbens is implicated with conditioned motor responses:  When you’re afraid, you feel fear and run away  Going to church and exercise makes you feel good  Gambling: stimulates the Nucleus Accumbens and makes you feel good. Nucleus Accumbens can make you do things that are good for you, but can also be inappropriately stimulated with pathology.

Case Studies: 1.

PTSD: a 26 year old is mugged, and he activates the panic button on his car. Nobody comes to help him, and he’s beat up and gets his wallet stolen. 3 months later, he is walking about of a parking lot and hears a panic button on a care. He instantly feels fearful, and he has vivid recollections of his mugging and he runs to his car. He then has nightmares for weeks. If the amygdala over-tags a stressful stimulus, even the slightest remembrance of that stimulus will lead to Amygdala firing. a. Presentation: i. He experiences an event where his life or someone else’s is in imminent danger, and they feel fear, horror, and helplessness. ii. Recollection: they experience nightmares, intrusive thoughts, or flashbacks. iii. Avoidance: they attempt to avoid things that remind them of the trauma and emotionally distance themselves from others. iv. Arousal: they experience an exaggerated startle response, poor sleep, and feel hypervigilant. Mechanism: Memory of trauma is stored in the amygdala. When the car alarm triggers, the trauma is re-experienced due to the sound   Cortex  Amygdala recalls the threat  Hypothalamus  Locus Ceruleus (Norepinephrine) and through Anterior pituitary (to cortisol to adrenal cortex to medulla to more norepi)

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This all leads to fear, anxiety, and autonomic activation.

Treatment: SSRI’s can help manage the anxiety, and group therapy can help normalize the feelings. -

Sleep agents can sometimes be used, and Prazosin (alpha-1 blocker) can inhibit Norepinephrine release during sleep and minimize nightmares.

2.

Generalized Anxiety Disorder: 22 year old student has daily unfounded worries about passing her examinations. a. Presentation: For at least 6 months, she experiences daily excessive anxiety, and she has difficulty in controlling the anxiety and can’t relax or cope. She always feels wound up and tense, is easily fatigued, and has problems with concentration, irritability, and difficulty with sleep. b. Mechanism: the primary NT’s associated with anxiety are Norepinephrine an Epinephrine. Serotonin directly inhibits these neurotransmitters. Anxiety is both cortical (anxious thoughts) and peripheral (hormone activation.) c. Treatment: focuses on increasing Serotonin and diminishing the ANS: Beta Blockers and Benzodiazepines.

3.

Frontal Lobe Injury: a previously shy 32 year old elementary teach suffers a significant concussion in a motor vehicle accident, and in the following weeks she is seen to be dancing on the dinner table at Chili’s, attempting to gain tips. She continues to display outrageous behavior and reactive behavior over the ensuing months: a. Mechanism: The frontal lobe manages executive function: planning and decisions, impulse control, and mood. After a traumatic brain injury, chronic drugs, or a stroke, the damaged frontal lobe leads to impairment in judgment. (Orbitofrontal cortex). A previously reasonable person will now act wildly without restraint and have difficulty controlling emotions. b. Treatment: medications that inhibit mood swings (valproic acid) and improve impulse medications (dopamine blockers, antipsychotics). Addition: classically the basal ganglia is associated with movement. Abnormalities are associated with repetitive actions, like OCD, where the caudate is abnormal and unable to stop hand washing or other behaviors. The primary neurotransmitter involved in the Nucleus Accumbens is dopamine, and this is a strong pathway for reward. Consider the basal ganglia in this case to relate to reward (dopamine) for repeated behaviors (basal ganglia). Addiction is associated with continued dopamine stimulation in the Nucleus Accumbens. a. Treatment: May focus on blocking reward pathways (block opiate receptors) or block dopamine (antipsychotics). Medications that are calming may reduce anxiety related to cravings (GABA-enhancing medications like the mood stabilizers.

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