The limbic system, emotion, the hypothalamus, appetites Flashcards
What is the function of the limbic system?
The limbic system processes emotion and related brain activity, memories, environmental cues and state of the individual and acts on this information to maximise survival, strategies
(we are not 100% sure though)
What structures make up the limbic system?
Core processing components;
- Amygdala = emotion
- Hippocampus (+cortex) (H.formation) = memory
- Septal area/nucleus accumbens
- Thalamus
- Limbic cortex (cingulate gyrus + Insula)
Effectors (output);
- Hypothalamus
- Brain stem structures
What is the Amygdala ?
Found in the anterior temporal lobe at the tail of caudate nucelus and rostral to hippocampus (deep in temporal lobe)
Grey matter blob with central, corticomedial and basolateral nuclei
What is the function of the Amygdala and what is Klüver-bucy syndrome ?
Klüver-Buucy syndrome is a rare syndrome in human produces behavioural impairment associated with damage to the anterior temporal lobes, including the Amygdala. Experiments in monkeys also show this.
Common affects;
- Hyperorality
- Placidity (lack of fear)
Rarer;
- Hypersexuality
- Visual (and other sensory) agnosia (recognising)
- Hypermetamorphis = excessive attentiveness to visual stimuli
- Memory loss
- enhanced aggression and anger
- Seizures
- Dementia
Causes;
- Heroes encephalitis
- Trauma
- Tumours
- Hypoxia
- Pick’s disease
Treatment is symptomatic and may include the use of psychotropic medications
What is Urbach-Wiethe (SM046) disease?
This more specific damage to the amygdala abrogates fear
Its a rare recessive genetic disorder including calcification in both temporal lobes caused by amygdala to degenerate in half the cases
A patient with this lived without fear, even when held at knifepoint had not a tinge of panic. She’ll happily handle live snakes and spiders although she claims to not like them
What are the structural features of the Amygdala ?
Amygdala has sensory input and drives responses through its output
corticomedial nuclei
not very well developed
in human but connect
with olfaction/gustatory
networks — may regulate
emotional responses to
food/smells)
What inputs into the Amygdala?
Input cane extant object (sensory), imagined or contextual
Aka can be from outside or inside the CNS
1). Stimulus -> view of snake (visual)/hiss of snake (auditory)
- Take a fast-track pathway via thalamus - doesn’t reach consciousness (e.g subliminal short route)
- Longer (conscious) route via cerebral cortex (e.g visual cortex)
2). Concept -> Idea of snake/memory of snake (via cerebral cortex)
3). Context -> Snake in the room via hippocampus
Inputs Go into the Lateral Nucleus of the Amygdala
Output from central nuclei
How does the Amygdala learn a modified fear response (emotional memory) ?
Amygdala can learn a modified fear response (emotional memory);
- If noise or scene is repeatedly associated with a fear stimulus, then it can elicit fear
- This could also be the context of the fear (e.g place or situation of fearful stimulus)
- This learning happens in amygdala (distinct from hippocampal memory)
- This is Pavlovian type of conditioning
Lateral nucleus responds to stimulus pairing (inputs)
Central nucelus then drives responses via two main centres which are the Hypothalamus and brainstem
THEREFORE, the basolateral amygdala compare incoming sensory stimuli (conditioned stimuli, CS, e.g tone, light, smell or context) to previously learned aversive (unconditioned stimuli, US, e.g fear/pain)
What does the Amygdala output from the brain ?
Amydgala outputs to hypothalamus and elsewhere via stria terminalis (another C shaped structure, ends in septal area, hypothalamus and BST - not shown)
Further Amygdala output to a variety of brainstem centres;
- Periaqueductal grey matter (PAG)
- Locus coeruleus (LC)
- Parasympathetics (solitary nucleius, dorsal vagal nucleus)
- Ventral tegmental area (part of the reward system)
(Just need to know there’s some targets here)
Give a general summary Amygdala ?
Amygdala summary;
- Controls emotional reactions (e.g threat/fear) via effectors (hypothalamus, brain stem through to the autonomic nervous system, endocrine and motor system)
- Emotional learning resetting according to threat level and experience (memory)
Responds directly via thalamus without cortex to measure size of stimulus
In emotion processing is there a higher level or cortical control ?
The Amygdala stores simple codes of value (valency; good/bad) for a threat/emotional trigger is there a more refined mechanism for evaluating the survival value of the emotional response?
CINGULATE GYRUS!
What are the features of the Cingulate Gyrus?
It has an anterior (ACC) and anterior portion of middle (MCC) involved in emotions = limbic cortex
(remember the insula is part of the limbic cortex)
ACC and MCC have connections for emotion as well!
ACC directs connections with amygdala and to effectors in brainstem (behaviour/ANS) MCC to motor cortex (movement and behaviour)
How has fMRI revealed the different parts of the limbic cortex in processing emotion?
Anterior cingulate encodes basic emotions - happiness, sadness and fear and emotional memory (so more than just fear)
Anterior cingulate has a top-down influence - works to recode the amygdala;
- computes relevance/outcomes - drive appropriate behaviour
- Provides conflict resolution (dorsal ACC e.g self vs non self in threat)
- Part of pain network - thalamus, primary somatosensory area and insula
What effector pathways does the limbic cortex have for emotion ?
Anterior and middle cingulate regulate complex interaction between unpleasant cues/pain emotions and avoidance behaviours and response, Work through the amygdala and directly to brainstem/motor cortex
- Motor reactions complex and context dependent (approach/avoidance behaviour; desire to leave the room; vocalization: facial expression; kissing; lip puckering; pushing)
Specific zone for driving face muscles
Direct outputs from ACC to autonomic system (direct to BS— dorsal motor nucleus of X and the nucleus of
solitary tract). Also indirect via the amygdala.
What is the anterior cingulate cortex (ACC) features?
The ACC (with some MCC) is considered to be the primary limbic cortex - higher order processing of emotion (top down with amygdala)
Features;
- has reciprocal connections with amygdala
- Heavy direct connections to autonomic centre including brainstem (bypass amygdala)
- Classified as the primary limbic cortex
- Attentional system, monitors conflict and resolves it
- Pain actives complex interaction with emotion here
- Motivates behaviours, mediates orientation towards or away from emotional stimuli
- Recodes value of stimulus on amygdala
What is the Insula?
Insula (anterior portion) works with the ACC in evaluating emotional contexts - role in empathy
Features;
- Connected to ACC
- Anterior portion considered to work with ACC
- Input -> visceral sensory information including pain
- Patients with lesions have defects including in awareness of other peoples pain (empathy)
- Classified as limbic “sensory” cortex
Encodes “emotional awareness”
How does the limbic cortex interact with the rest of the brain for higher order emotion processing?
Image
How does PTSD affect the limbic system?
- Part of ACC is hyporespontsive in PTSD
- Reduction in size of ACC
- Amygdala becomes hyper-responsive to trauma related stimuli
- Top down control by ACC is therefore missing in PTSD
Give a brief summary of the function of the Cingulate gyrus?
Cingulate gyrus Summary;
* Emotion response regulation coordinated via connections with the amygdala
- Makes prediction about negative consequences resolves conflicts
- Top-down regulation “recodes” the amygdala processing/responses
- Drives conscious responses to unpleasant experiences
- Drives avoidance behaviours and motor such as facial expression (from MCC to motor cortex)
- Also has direct influence on Limbic effectors (ANS) by-passing amygdala
- Works with insula which provides wider context of awareness to unpleasant especially visceral
stimuli (empathy; pain)
What do effectors and regulators in the limbic system do and what are they?
The effectors and regulators in the limbic system;
- Mediate emotional reactions (behaviour and physiology) via ANS
- Modulating learning/settings of Limbic system resetting according to conditions/memory
They are;
- Hypothalamus
- Locus coeruleus
- Periaqueductal grey
- Dorsal Raphe Nucleus
What is the hypothalamus’ function in the limbic system?
The hypothalamus is a major effector of the limbic system
It has direct input from limbic cortex, amygdala (but reciprocal)
Input from olfactory, sensory systems (pain), visceral, retina, internal signals
Output neuronal to brainstem, spinal cord, and via hormonal control
What is the Locus Coeruleus function in the limbic system?
- Midbrain nucleus involved in physiological responses to panic and stress
- Input from CG, amygdala, PAG and hypothalamus
- Noradrenaline fibres projecting from nucleus to widespread brain structures
- Promotes alertness and wakefulness (widespread connections)
- Promotes anxiety + formation and retrieval of emotional memories (amygdala) - dense projections from LC to amygdala
- Projections to hypothalamus from LC maintains arousal and also effect autonomic nervous system output
- Projections from PAG selects fight or flight mode
What is the Periaqueductal grey (PAG) function in the limbic system?
Its a limbic effector as well as a co-ordinator of fight/freeze/flight responses
Part of the pathway that mediates LIMBIC autonomic reactions (e.g, fear, pain, analgesia)
Inputs from cingulate gyrus and amygdala
Projects to nucelus of solitary tract, dorsal nucelus of vagus, intermediolateral column
Projections from PAG to LC selects fight or flight mode
PAG has multiple modes/pathways;
Defensive fear networks - fight, freezing or flight
- Amygdala -> ventrolateral (vL) PAG -> vagal paths (parasympathetic in freezing)
- Amygdala/CG -> dorsalateral (dI) PAG -> LC and Bstem (fight or flight switching)
Pain network (refer to ascending pathways)
- Pain regulation -> encephalin -> raphe nuclei -> 5HT dorsal horn -> interneurons block pain paths
How can threat response vary?
Threat response depends on context
e.g if snake is close or far away you will have different responses
Far away - Cingulate gyrus (CG) processes response through basolateral amygdala to striatum (PAG independent)
Close by - Central amygdala (CA) drives PAG and other brainstem centres to panic/freeze mode
What is the function of the Dorsal Raphe nucleus (DRN)
Dorsal Raphe nucleus (DRN);
- midbrain nucleus project an ascending
- Projects to and receives from amygdala and ACC
- 5HT (serotonin) neurons
- Determines tonic limbic activity, may regulate dynamic mood state
- Also processes descending pain paths from PAG and DRN to spinal cord
What is the theory of 5HT used in drug development and how can changes in the limbic system establish depression?
Theory of 5HT (serotonin) depression/mood in (basics for drug development)
Changes in limbic structures in established depression;
- Reduced metabolism in ACC
- Reduced size of ACC
- Amygdala hyperactive and medial output region increased in size
Is there any predispositions that may be more likely for someone to develop depression?
In normal individuales with;
- Varient polymorphisms in 5HT transporter gene (5HTT)
- Diminishes transcription efficiency and expression
- Possible increased risk of depression (especially in reaction to previous stress)
- Reduced communication between ACC and amygdala
- Reduced size of amygdala and increased reactivity of amygdala to emotional stimuli
How may abnormalities in reward circuits affect people?
amygdala pathways overlap with those that regulate reward
Reward centres are located in the nucleus accumbent and prefrontal area
Amygdala is connected to the ventral striatum (Nuc accumbens) via stria terminalis
In some types of depression blunted activation of the reward centres (image attached)
Suggests targets for deep brain stimulation nucleus accumbens
What is the hippocampus and associated cortex (hippocampal formation)
Now considered by some not to be a LIMBIC system structure
Has only an indirect influence on emotion
But important function in establishing episodic memory
How does the hippocampus play a role in memory limbic system ?
One of the most throuoghluy investigated structures in the brain
- HM patient case study stimulated investigation in memory
- Site of discovery of LTP, the basis of major theories of memory
COMBINES SPATIO TEMPORAL INFORMATION WITH;
- emotional
- sensory
- cognitive function
Including memories for locations and events at those locations
Where is the hippocampus found and what does it look like?
- Deep in temporal lobes
- Elongate structure in the floor of the lateral ventricle
- Name reflects its similarity to a seahorse
- Rolled appearance
- Evolutionally old cortex
What is the hippocampal formation?
Hippocampus and associated cortex (parahippocampal gyrus) together make the hippocampal formation
Features;
- elongated structure
- entorhinal area (rostral) is the main gateway for communication (input) with the neocortex
- Subiculum most inferior portion of hippocampus
- Subiculum connected to entohinal areas, amygdala and nucelus accumbens
- Dentate gyrus characteristics circuitry + 4 CA regions in cornea ammonia
What are the functions of the hippocampus ?
Hippocampus plays a critical role in memory formation by providing the brain with a
spatiotemporal framework within which the various sensory, emotional, and
cognitive components of an experience are bound together.
This framework allows the experience to be stored in such a way that it can be later
retrieved as a conscious recollection of that experience.
What its the basic trisynaptic circuit in the hippocampus (proposed learning circuit)
Image
What are the 3 inputs into the hippocampus through related cortex for memory processing ?
PLACE
THINGS
EMOTIONAL INFORMATION
How can disease in the hippocampus manifest ?
Disease in the hippocampus;
- Sensitive to stress (glucocorticoids)
- Cushing’s disease and glucocorticoid administration
- Ischemia sensitive
Atrophy in the hippocampus is found in;
- Alzheimer’s disease (change in size and function of hippocampus - early detection using multiple biomarkers is being assessed but not established yet)
- Wlliams syndrome (1/10,000 births) genetic deletion syndrome in which there is developmental hippocampus effects
- Chronic alcohol use has detrimental effects on hippocampus related learning and causes damage there. Dose dependent negative correlation of hippocampus size and non-dependent moderate alcohol consumption over 30 years.
(Wernicke-Korsakoff syndrome - thiamine deficient alcohol related hippocampal damage and decrease in hippocampal learning) - Hypertension
- Depression
- Epilepsy
- Cushing’s disease
- Stress (PTSD)
- Genetic disorders
What is the Fornix?
A major output tract of the hippocampus involved in memory
The Fornix projects to the mammillary bodies which are connected to the anterior nucleus of the thalamus (damage to the fornix and these two structures can cause memory problems)
What are the functions of the fornix?
See different tracts in image - output segregated according to hippocampal processing (rostral/caudal)
Glioma in wall of the lateral ventricle
displacing both fornices
23-year-old woman who presented
with progressive headaches
over a 2-month period.
Memory deficits delayed recall for
verbal and visual-spatial info.
120 mm
