Slackers Guide: Limbic, Memory, Prefrontal Cortex V2

1. Slackers Guide: Limbic, Memory, Prefrontal Cortex V2 Prepared by Mike Ori

2. Disclaimer • Slackers please continue but note… • The summary was taken from our class notes and PowerPoint slides. They reflect my understanding and could be wrong. • The faculty has in no way vetted this document. • I’m really uncertain of anything with (?) or in red. • If you see something wrong, let me know. If you’re a gunner, shame on you for looking at this. Do your own work.

3. Function Map • On the next slide is a functional representation and interconnection map for many of the anatomical structures we have learned in class. On subsequent slides, I break the function out in more detail and try to ascribe anatomy to it. • The totality of the reciprocations and interconnections is not complete as … • I am lazy • It would have been really messy

4. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Motivation & Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

5. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Current Physiologic State Memory: Emotional Content • CNS Input • Parasympathetic visceral afferents afferents from CN V, VII, IX, X • Sympathetic afferents arrive via cranial SPINAL nerves with collaterals to NTS • Received in brainstem nuclei (nucleus of solitary tract) • Handed to the parabrachial nuclei for amygdala and hypothalamus • Handed to the thalamus for insular integration and primary reception • Limbic structures • insula, amygdala receive and process this information in order to provide emotional feedback to the body’s physiologic state. • The insula raises this information to conscious awareness and can push conscious state downward via outputs to autonomic regulation centers (no autoniomic regulation is not conscious) • The ACC affects the physiologic state by amygdala reciprocation and via direct brainstem connection Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning spinal cord

6. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Sensory Focus Vigilance Attention Memory: Emotional Content Social Awareness Sensory Input • Amygdala output enhances brain functions across the board when a threat (or anything significant) is perceived. This feedback focuses our attention and increases alertness and processing efficacy in all cortical areas. It is carried by acethylcholine (nc. basalis) and norepinephreine (locus coeruleus). • Amygdala feedback to sensory systems enhances function and distorts perceptional awareness to increase sensory perception on threats. • Insular outputs (reciprocated) can similarly affect these systems (all, partial, none?) • Norepinephrine, acetyl choline (ARAS) projections, and histimine affect our alertness via distributed, wide-spread innervation of the entire cortical mantle Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

7. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Sensory Input Memory: Emotional Content Social Awareness Sensory Input • Sensory input arrives from special afferent into primary areas. • Primary visual (occipital -> dorsal (where) and lateral (what) ) • Somatosensory (Secondary somatosensory of insular cortex maps of affective sensation) • Auditory (temporal) • Gustatory (NTS -> thalamus -> insula) • Olfaction (Olfactory Cortex -> orbital PFC cortex and insula) • The limbic components come from all areas of input stream processing from raw to highly processed. (note this is a fuzzy statement on my part) The limbic consumers of this data are the amygdala and the insula, and the Insula and the OFC • Information streams from primary -> unimodal -> multimodal areas • Lesions in primary areas result in agnosia (complete?) in a portion of the sensory field. • Deficits in unimodal areas result in agnosia for a specific submodality • Multimodal defects result in cognitive defects to understanding the meaning of the sensory data. (Can see brown, hairy and can hear barking but can’t conjure dog) • The parietal lobe maps and relates(?) the world around us and relates it to the position of our body or body parts is space. The posterior cingulate also plays a role in spatial understanding of the environment especially concerning eye scanning and processing sensory inputs created by one’s own movements. So does the hippocampus. Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

8. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Memory: Factual Acquisition Memory: Emotional Content Social Awareness Sensory Input • Explicit (Declaritive information: facts, events, people) • Require deliberate conscious effort to recall - like things you might memorize • During wakefulness, the hippocampus stores factual data. It is believed that this information is consolidated and stored in the cortex during sleep. The cooperation of the amygda is valid only for emotionally significant events. • Damage to the hippocampus, parahippocampalgyrus, entorhinal cortex, and multimodal association areas of the temporal lobe results in anterograde amnesia. • Amygdala input provides enhanced learning during emotional situations • The posterior cingulate provides data to the hippocampus on spatial orientation (Parietal, PCC interaction? yes, involving many other areas that you do not need to know for the exam) • Working memory is processed in the dorsolateral PFC. Working memory is like RAM on a computer whereas long term memory is like the hard disk (BINGO!). We have to call things up from long term storage to work on them (consciously anyway). Think about an elephant. • Retrograde amnesia is usually the result of degenerative or traumatic processes to the cortex. • The hippocampus will store the mechanical details of an amusement park ride but will not associate the thrill of the ride (yes it could, if the amygdala plays along) remember memories about emotions vs emotional memoies the difference is the contribution of the amygdala) • Implicit memory (non declarative: dexterous skills, intangibles like strategy and rules) • Does not require conscious effort to recall – riding a bicycle • emotional memory - Amygdala • Skills – cerebellum, motor cortex • Conditioned reflexes - cerebellum Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

9. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Memory: Assessment & Consolidation Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • Data stored in the hippocampus is replayed during sleep • Amygdala input associates emotional importance. Increased amygdalar activity enhances the consolidation of emotionally important (negative) memories and is implicated in PTSD. • Memories that are of sufficient quality are consolidated and stored in the cortex • Body state signaling from high stress states increases storage efficiency in the short term due to ascending visceral and hormonal signals and via norepinephrine. Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

10. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Memory: Emotional content Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • The amygdala determines the emotional state of events, places, things, etc. Based on the emotional content, the amygdala will increase the efficiency of consolidation of the memory. • The amygdala would associate the thrill of an amusement park ride but not necessarily the details of the machinery (yes) • Amygdala damage diminishes emotional content storage but not factual content. • The amygdala is responsible for conditioned response in which a neutral stimulus is tied to a positive or negative response in the body’s state. • Emotional learning can occur with a single exposure to a stimulus if the stimulus is great enough. Norepinephrine release from the locus ceruleus enhances emotional learning. Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

11. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Integration of consciousness and viscera Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • The insula acts as a gateway to the consciousness for many emotional responses. • Flavor • The insula receives input from and reciprocates output to • Sensory afferents in various stages of processing • Visceral afferents • Amygdala afferents • Without the insula, sensations will be registered without emotional valence. • The irritation of an itch and the relief of scratching • The punishing nature of pain • The insula bonds emotional content with the same physiologic state to the proper conscious emotional state. Stage fright vs first kiss. yes Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

12. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Emotional Content Assessment Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • The basolateral amygdala assesses the emotional significance of the situation and the centromedial nucleus effects the changes in the autonomic system and signals the emotional state to other limbic and cortical structures. • Situation can be assessed as either good, neutral, or bad • Reciprocated projections turn up or turn down(we do not know about down) the processing of the cortical area as well as the autonomic area via effectors in the centromedial nucleus. • Inputs from the ventromedial prefrontal cortex influence the analysis performed by the amygdala and can force an emotional reappraisal of the event. Reappraisal alters the amygdala’s output. • See the maps at the end for amygdala connections Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

13. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Physiologic Control Memory: Emotional Content Social Awareness Sensory Input • The body’s physiologic state is controlled by centers in the brain stem and by the hypothalamus. Both of these are influenced by emotional state. • The hypothalamus is the principal monitor and effector of the body’s visceral state state. • projects to various portions of the brain stem and can alter the activity of these centers • Has various direct and indirect sensory inputs • Direct are from periventricular organs and temperature sensing neurons • Indirect are from remote sensors like baro receptors and remote temperature sensitive neurons. • Limbic controls • amygdala (centromedial) impact both the hypothalamus and the centers in the brain stem. These projections provide powerful inputs that can adjust the body’s state quickly in the face of emotional distress. • Insular inputs can similarly modify the body’s state • Multiodal cortical regions indirectly affect physiologic states through the amygdala ceontromedial nucleus Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

14. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Memory Storage Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • Explicit • Several cortical areas work together store long term memory. Memories are probably parceled out all over the cortex in areas specialized for the remembered modality. • Memory is associative and systematic. Meaning its easier to learn about things you already know about than something entirely novel and that associating information with other better known memories will enhance it storage? Yes, indeed. Knowing the rules of the game makes a better player • Explicit memory is recalled into working memory? YES • High stress levels affect the hippocampus (neurotoxic degeneration) and result in decrease explicit memory storage. In contrast, these same stress signals enhance emotional storage. • Implicit memory is stored in the amygdala, the motor cortical areas, and the cerebellum Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

15. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Social Awareness Memory: Emotional Content Social Awareness • Amaygdala • crucial for recognition of facial emotional content after processing by various facial recognition centers (in medial temporal lobe and elsewhere?) Fusiformgyrus • Responsible for setting emotional state that guide decision making but can be overridden by the ventromedial PFC if an action would not be worth the cost. (PFC says, its rarely worth dressing down your boss regardless of amygdalar desires) • Insula • provides empathy centers for pain • Facial recognition of disgust and trustworthiness • Anterior Cingulate • The affective portion regulates mother-infant relations (positive or negative social development?) Look at the Autism lecture. • Prefrontal cortex • The dorsolateral PFC understands the rules that bind society together and formulates strategies in conjunction with judgment of the cost/benefit from the ventromedial PFC. Together these cortical areas regulate many aspects of personality that directly relate to social personality. Phineas Gage’s personality change and generally antisocial behavior was the result of VMPFC damage. He understood the social rules but just couldn’t calculate their impact. • Supervisory aspects of the PFC prevent us from activating socially inappropriate behavior Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

16. You can’t make a strategy if you don’t know the rules. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Consequence Assessment and Planning Memory: Emotional Content Social Awareness Sensory Input • PFC in general • Perseverenceerrors and lack of flexibility in planning, reasoning, cognition • Deficits in the PFC may create a depressed state in which a person is aware of a conflict between what they would like in their lives and what they receive but they are unable to figure out how to change this, because they cannot initiate action. their depression but is unable to initiate action to relieve it. • Dorsolateral PFC • Rule application and strategy development • Flexibility in rule changes • Ventromedial prefrontal cortex • processes social factors and reward/loss (cost/benefit?) especially as they relate to time. In business speak it calculates return on investment (ROI). Note that short term rewards are limbic (VTA, amygdala) • Errors in strategy, planning, and judgment can arise indirectly from remote lesions in PFC interconnecting areas such as the basal ganglia and thalamus (dorsomedial nucleus). The disconnection of these structures is called diaschisis. Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

17. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Outcome Monitoring Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera • The outcome of an event is monitored by the anterior cingulate’scognitive area. • If an outcome differs from the expected outcome, a change in the firing rates of dopamine projecting neurons in the ventral tegmental area occurs. • The detection of outcome variation is detectable via an EEG in a characteristic variation in activity called the ERN (error related negativity). An ERN will appear for any variation (error) from the expected reward so both too much and too little reward activate an ERN. • Abnormally high ERN are seen in OCD and anxiety disorders • Abnormally low ERN are seen in drug abuse • Typically motor movements and decision making will slow down after an error is detected. • Abnormal amygdala activity can influence the ACC in that a hyperactive amygdala will make the system more pessimistic and hence make rewards less rewarding. I am not sure about this • The PFC reprocesses the significance of events when an error occurs. Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

18. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Value learning Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • The amygdala and the ventromedial prefrontal cortex both play a role in value learning. The amygdala understands value of short term reward whereas the VMPFC understands value in the long run. Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

19. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Memory Retrieval Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • Emotional • The amygdala stores conditioned stimulus memories and can adjust the body’s state from the recall of these memories. • Input from the prefrontal cortex can suppress the action of emotional memories by inhibiting amygdala evaluation (basolateral) and action (centromedial) in a process called extinction. Multiple exposures are required for extinction to occur. The memory remains latent and may reemerge in full force in the proper circumstance. • Implicit skill based memory cannot be recalled (easily? accurately?) recalled at allinto consciousness. Think about how you ride a bicycle – you don’t want consciousness involved in each function. • Explicit memory must be loaded from its remote storage sites in the cortex into working memory YES Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

20. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Initiation & Motivation Memory: Emotional Content Social Awareness Sensory Input • The ACC – Congitive portion • Responsible for initiating actions and influences various motor responses • Visceromotor • Skeletomotor • Motor prepardness (not sure what this means) a pre-activation that will facilitate the real activation when it comes and reduces reaction time – think about tennis – you ready your racket in an optimal position when you are served not only when you need to respond • Emotional motor behaviors (defensive postures, freeze to threat, etc THIS IS DONE VIA THE PERIAQUEDUCTAL GRAY) • Planning action comes from the dorsal lateral prefrontal cortex but motivation to perform action comes primarily from the affective ACC (and its basal ganglia loop). • ACC deficits may create a depressed state in which the person lacks the will to change. • Amygdala Centromedial input to the basal ganglia affect movement. • The insula plays a role in oral behaviors and addictions and damage to it can reduce the motivation for behaviors such as smoking. Integration of consciousness and Viscera Consequence Assessment and Planning Initiation Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

21. Memory: Factual Acquisition Memory Assessment & Consolidation Memory Storage Memory Retrieval Outcome Signaling Memory: Emotional Content Social Awareness Sensory Input Integration of consciousness and Viscera Consequence Assessment and Planning Initiation • EXPECTATION AND Outcome are signaled by dopamine releasing neurons in the ventral tegmental area • ERROR signaling neurons in the VTA project to many areas of the brain including • Basal Ganglia (nucleus accumbens) • Subcortical and cortical limbic structures • Prefrontal and orbital cortex Sensory Focus Vigilance Attention Emotional Content Assessment Outcome Signaling Outcome Monitoring Current Physiologic State Physiologic control Value Learning

22. Amygdala Basolateral Connections Fig. 4. Reciprocal connection of the basolateral nuclei of the amygdala with cortical regions. A. The basolateral nuclei receive highly processed, multimodal sensory information from the association cortices of the temporal lobe (yellow arrows) and reciprocate these inputs (red arrows). B. The basolateral amygdala sends feedback projections to the earliest stages of sensory processing. The yellow arrows indicate the multistage visual processing (ventral visual stream) starting at the primary visual cortex . The red arrow shows feedback connection from the amygdala to the primary visual cortex. C. The amygdala is reciprocally connected to the medial and orbitofrontal areas and to the cingulate cortex.

23. Amygdala Centromedial Connections

24. Insula Connections

25. Anterior Cingulate Cortex

26. PFC Loops