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Give an overview of the anatomy of the limbic system

Areas are functionally (rather than anatomically) related

Cortical regions: prefrontal, cingulate, insula, parahippocampal gyrus

Subcortical regions: hippocampus, amygdala, ventral striatum


Describe the neuromodulatory pathways using norepinephrine, dopamine, serotonin (5HT), and acetyl choline.

NE: works with 5HT, projects from locus ceruleus to cortex, attentional selectivity during stress

DA: projects from ventral tementum to PFC/BG, promotes motivationally-based behavior

5HT: projects from raphe nucleus to cortex, mood and sleep-wake cycle

ACh: septum, nucleus basalis, diagonal band of Broca to thalamus and cortex, drives laying down of memory


What are the regions of the prefrontal cortex and their functions?

Lateral PFC: working memory, executive control, choosing an option

Orbitofrontal: reward, motivation, emotional decision-making, inhibition, changing your mind

Ventromedial: emotions, memory, habits
Medial (of VM): incorporates emotions in decision-making
Anterior cingulate (of VM): choosing among complex actions


Describe the location, connections, and overall functions of the hippocampus.

Near the surface of the medial temporal lobe, bulging into the lateral ventricle.

Hippocampus--Entorhinal cortex--Perirhinal cortex--Parahippocampal cortex

Afferents: from sensory, association, cingulate, and prefrontal cortex
Efferents: to wide areas of prefrontal, temporal, and parietal cortex

Temporarily stores declarative memory and consolidates it into cortex.


Describe the role of the hippocampus and vmPFC in forming and consolidating declarative memory. Where is declarative memory stored?

The hippocampus temporarily holds declarative memory while consolidating it to wide areas of cortex.

Declarative memory is stored in various areas of neocortex, but especially in vmPFC.

Episodic memory: medial prefrontal, parahippocampal, entorhinal, perirhinal, lateral temporal, and parietal sensory association cortices.
Semantic: anterior temporal lobe, lateral prefrontal cortex


Describe the stages of sleep and their EEG correlates. Compare SWS and REM stages of sleep.

Sleep deepens through 4 stages, during which the EEG waves increase in amplitude and decrease in frequency. Larger waves (SWS) indicate more synchronicity due to blocked sensory input and VLPO inhibiting the arousal system. =Inactive mind in an active body. Dominates first half of sleep.

REM sleep has an EEG similar to awake. Excitation of thalamo-cortical activity and visual cortex. High brain activity but transient paralysis. =Active mind in an inactive body. Dominates second half. Two stages differ by reactivity to sound.


What are the pathways that maintain wakefulness, and how do you fall asleep?

Wakefulness is initiated and maintained by pathways from the reticular formation to the thalamus (ACh-pons) and cortex (NE-locus ceruleus, 5HT-raphe, DA-PAG, ACh-basal forebrain, orexin/hypocretin-lateral hypothalamus)

Sleep is initiated by the VLPO of the hypothalamus via inhibition of all arousal nuclei to induce drowsiness.


Describe how memory is consolidated in sleep: When does reactivation of memory occur during sleep? When are memories consolidated?

Declarative memories are reactivated and consolidated during SWS, coinciding with the slow wave peaks. They can also be reactivated during wakefulness or REM sleep, but with different results.
Cortical slow waves alternate with hippocampal activity spikes, indicating that movement from hippocampus to cortex and from cortex to hippocampus (the processes of consolidation) do not happen at the same time.


What role do the septum and diagonal band of Broca have in memory consolidation?

The septum pellucidum and diagonal band of Broca are responsible for theta waves, which separate new memories being encoded from old memories being recalled.


What sleep-wake conditions optimize memory consolidation?

Declarative memories consolidated during waking are labile and easily disrupted by other incoming information.

Memories consolidated during REM sleep are subject to major restructuring, revealing unique insights and correlations.

Memories consolidated during SWS sleep are stabilized in their original form.


How is memory consolidation affected in Alzheimer’s disease? Bilateral hippocampectomy?

Alzheimer's involves degeneration of cortex, cholinergic, and other neuromodulatory tracts, resulting in the inability to consolidate short term memory into long term.

Bilateral hippocampectomy removes the individuals short term memory storage, so nothing is retained beyond working memory.


How are emotional experiences manifested? What role does the amygdala play in expressing these manifestations?

There are three manifestations of emotions:
1. ANS/physiological e.g. blood pressure
2. Behavioral e.g. facial expressions
3. Subjective feelings or drives e.g. love and lust

The amygdala regulates behavioral and visceral functions, especially in response to ambiguous stimuli (like scared faces).


How do the efferent pathways from the amygdala generate affective/emotional attention?

Ascending projections go up into the cortex and shapes information processing and memory consolidation. This happens via basal forebrain.

Descending projections go through the hypothalamus and lead to activation of ANS visceral responses like increased HR. This happens via various brainstem nuclei.


What types of facial expressions do the amygdala respond to and why?

More responsive to ambiguity, when gathering more information is important. Responds less to angry faces, more to fearful or surprised faces--they require vigilance. Vigilance is maintained via basal forebrain using acetylcholine.


What is emotional memory? Describe conditioned fear and extinction and what brain areas generate them

Emotional memory is an unconscious emotional response to stimuli that proceeds independent of conscious attention.

Conditioned fear is an example of emotional memory. An animal is trained to have a particular emotional response to a stimulus (rats respond to beep with fear). This is accomplished by pairing an innocuous stimulus with a painful one, so that perception of the stimulus provokes anticipation (fear) of the expected event.

Amygdala receives information about what is happening to you and evaluates social and emotional significance, which is then projected back to mPFC, where hippocampus consolidates it using ACh. Extinction happens when the vmPFC, which is the voice of reason, inhibits the amygdala because it understands the fear in context.


How is the amygdala regulated in its expression of emotional responses?

The amygdala is part of a cue-processing system: it reacts to stimuli. This system works in balance with a context-processing system, which lets you understand the meaning of cues in a particular context. i.e. a snake is dangerous, but if it's at the zoo behind glass it doesn't pose a threat.
This involves: vmPFC, hippocampus, anterior insula, and anterior cingulate.


What does it mean that the amygdala retrieves emotional memories unconsciously?

The amygdala provokes emotional memory with or without conscious perception of the stimulus. For example, if a subject is conditioned to respond to an angry face and it is flashed on a screen very briefly before being replaced with a neutral face, there is no perception of the angry face but it does elicit an ANS response.


Compare memories of emotions vs emotional memories.

Emotional events are perceived by sensory systems and then stored in two ways. Memories of emotional events are sent to the hippocampus (cognitive representation of emotional situation). Emotional memories, the unconscious emotional response to stimuli, are sent to the amygdala.


How do high levels of NE and DA neuromodulation affect the relationship of prefrontal cortex and amygdala?

During stress, high levels of NE and DA impair PFC functioning and strengthen fear conditioning by the amygdala. A greater fear response coupled with lack of context-based inhibition produces anxiety or otherwise inappropriate negative emotions.


What is meant by top-down and bottom-up control of the amygdala?

Top-down control is the thoughtful, context-considering regulation by the PFC.
Bottom-up control is from the sensory cortices, which allow the attention to be diverted by whatever stimulus is most salient.
During stress our tendency is to switch to bottom-up control.


What effects do lesions of the vmPFC/OFC and of the amygdala have on behavior?

vmPFC lesions: lose inhibition of amygdala (left at the mercy of emotional responses) and ability to plan ahead.

Amygdala lesions: make you really stupid, don't understand what's in front of you and what you should do about it.


Describe the location and some of the functions of the insula.

Insula is located deep in the lateral sulcus. Anterior part perceives affective (emotional) aspects of pain and temperature, integrates body states into emotional processes. Posterior part handles somatosensory input to map internal body states.
Also helps modulate homeostasis in anticipatory response to novel stimuli or tasks.


What is working memory? Describe the dlPFC and its role in working memory.

Working memory is the ability to keep a thought in your head long enough to work with it. Also allows you to concentrate, inhibiting inappropriate responses and distracting stimuli.
The dlPFC is the main region involved in working memory. Networks of dlPFC pyramidal cells generate persistent activity, activating each other to keep the information in mind.


What is the significance of the prefrontal cortex’s ability to sustain activity over long periods of time?

Working memory is a property of consciousness: we can consider the immediate past, the present, and the near future all at once.


What is the role of NE and DA in maintaining working memory? What happens in the dlPFC if there is excess of NE and DA?

NE and DA neuromodulation sustain working memory:
NE increases response to preferred inputs (promotes attention)
DA decreases response to non-preferred inputs (sculpting attention)

Low levels of NE/DA = non-alert
Optimal levels = alertness, focus
High levels (stress) = too much activity therefore distractible (similar to ADHD)


What area of cortex is the development of each type of memory associated with?

Hippocampus & medial temporal lobe: declarative
Amygdala: emotional type of procedural memory
Prefrontal cortex: working memory


What is the anterior temporal system and what aspects of memories does it store?

Perirhinal cortex, temporopolar cortex, lateral orbitofrontal cortex, and amygdala.

Relates representations of specific entities to existing semantic concepts (like connecting face with name)


What is the posterior medial system and what aspects of memory does it store?

Parahippocampal cortex, retrosplenial cortex, posterior cingulate, precuneus, angular gyrus

Matches what you know about your context to what you might be able to do there (you know there's a coffee shop nearby and it's 3:00 when Maria gets off work, so you know you could meet Maria and grab a latte).


What is the retrosplenial area and what does it do?

Area of the cingluate gyrus, responsible for precise recall of episodic memory.


How is sleep regulated by a circadian cycle?

SCN responds to ambient light/dark, projects information to SPZ and DMH.
With light, DMH inhibits VLPO and stimulates orexin.