Affective neuropsychology

Emotion, learning & memory

Rostral (anterior) limbic system

Amygdala + septum + orbitofrontal cortex + anterior insula + anterior cingulate → emotion, regulation, analysis, survival significance

INPUT: PFC from amygdala

Caudal (posterior) limbic system

Hippocampus + posterior parahippocampal cortex + posterior cingulate → memory, declarative, navigation

INPUT: anterior nucleus from mammillary bodies
OUTPUT: anterior nucleus to posterior cingulate gyrus

Hippocampus sug-regions

Jam swirl = dentate
Cake swirl = hippocampus proper
↓
Subiculum
↓
Entorhinal cortex
↓
Parahippocampal gyrus
↓
Fusiform gyrus
↓
Inferior temporal gyrus (most lateral)

What parts of the diencephalon connect to the rostral (anterior) limbic system

• Hypothalamus (connects to septal area & amygdala)

• Anterior thalamic nuclei (anterior, dorsomedial)

What parts of the diencephalon connect to the caudal (posterior) limbic system

• Thalamus (lateral dorsal, pulvinar)

• Epithalamus (includes habenula, reward processing/aversion)

• Mammillary bodies (of hypothalamus, hippocampal input)

What is emotion?

A coordination of 3 neurobiological states:

1. Physiological (change in body state by ANS)

2. Behavioural (clear and observeable in animals, basic, evolutional circuitry, camouflaged in humans)

3. Feeling (unanswered, non-specific to senses, ‘conscioussness’)

causing a coordinated response triggered by the brain, a state of emotion

Major structures involved in the elicitation and evaluation of emotional experiences?

Limbic structures [connect cortex—hypothalamus—reticular nuclei]

AMYGDALA: emotional memories, significance of stimuli to feelings

HIPPOCAMPUS: declarative memories (factual, information)

Prefrontal cortex [social interaction-related emotions]

• Lesions impair empathy, pride, embarrassment, guilt (sociopathy)

• Directs appropriate social behaviours/relationships, moral decision-making, rewards, punishment

Cingulate gyrus [connects cortex and subcortical limbic regions]
mostly note anterior cingulate, highest emotional involvement

• Cognitive-emotional pain response

• Interacts with PFC and parietal

• Assigns emotional valence to stimuli, selects/maintains attention

• Hippocampal connections aid memory retrieval and storage

• Cingular motor areas (in limbic lobe), incorporate emotion into motor responses

Major structures involved in the physiological expression of emotional experiences?

Facilitated by the HYPOTHALAMUS + activation of the
→ subconscious and involuntary

1. Autonomic nervous system

2. Endocrine system

i.e., tests for arousal level including HR, body temperature, perspiration

‘Sham rage response’ in cats using regional brainstem electrode stimulation (doesn’t work with hypothalamic lesion)

Major structures involved in the behavioural expression of emotional experiences?

Facilitated by brainstem nuclei like the:

Periaqueductal grey [midbrain surrounding cerebral aqueduct]

• Central pattern generators (CPGs) for swallowing, phonation, defensive behaviours, vomiting, facial expressions

• Processive aversive and appetitive stimuli

• Pain perception, emotional responses, sleep-wake cycle

Reticular nuclei [i.e., pontine & medullary reticular formations]

• Cardiovascular, respiration, urination, muscle tone, reflexes

• Stereotypic behaviours: species-specific/characteristic, from evolution

• Specialized, localized regions, also sleep-wake cycle

NOTE: facial expressions are not evoluntarily/behaviorally driven, the emotional ‘fingerprint’/circuitry in the brain differs vastly

What is emotion as an action tendency?

1ST LEVEL, basic emotions are:

1. Required for survival, occurred via evolution

2. Drive is embedded in neural circuitry (no learning required)

3. If essential = found in all animals with a brain/universal

4. Informs understanding of affective disorders

Limbic circuit connects primitive/automatic (thalami & brainstem) to higher association (cortex): interpretation, evaluation, emotional mearning

2ND LEVEL, subcortical areas:
→ near automatic, but learned, requires some processing (like amygdala)

3RD LEVEL, PFC and cingulate gyrus:
→ cognitive flexibility, requires environmental analysis and context-varied responses

Threat detection vs reward motivation

1. Fear/arousal level

   1. Reticular activating system (ascending), MONOAMINES

   2. Reticular formation (descending)

      • Internal and external stimuli input

      • Output direct to cortex or via thalamus

      • Regulates cortical electrical activity regarding arousal, sleep/wake, attention focus

2. Seeking circuitry

   • A general motivational drive, ‘feel good’ sensation’ to engage with the world

   • Under-functioning causes depression

   • Overactivity causes mania, addiction, delusions

List the monoamine brainstem pathways for endogenous chemical regulation of affective circuitry

1. Meso-limbic-cortical & other dopaminergic pathways (‘seeking’)

2. Serotonergic pathways

3. Noradrenergic pathways

Dopamine and meso-limbic-cortical pathways

Motivation to act, not the sensation of pleasure

Dopaminergic output from the VTA = ‘wanting’
Opiate action in nucleus accumbens = ‘liking’

Dopamine NT → record of what’s ‘good’ to increase motivation in future encounters

• Spikes immediately post-reward

• Spikes in anticipation (if predicted, prior to CS)

ALSO, learning and executive evaluation to execute long-term motivational processes. Facillitates:

• Goal-directed behaviour, behaviour flexibility

• Working memory, attention, inhibition

• Complex thoughts, adaptive social behaviour

*there’s an optimal DA level in the PFC, underactivity found in schizophrenia and ADHD

Serotonergic pathways

Monoamine neurotransmitter AND neuromodulator

95% found in periphery, a lot of autonomous functions:

• Intestinal movement, bronchoconstriction

• Platelets and vasoconstriction

• Mediates inflammation, sensitizes nociceptors
  

5% found in CNS from raphe nuclei (brainstem):

• Rostral projects to thalamus, striatum, cortex (sleep-wake, mood)

• Caudal projects to brainstem and spinal cord (pain pathways)

• Regulates mood, sleep, sex drive, cognition

NOTE core receptor types:

5-HT1A [limbic, amygdala]
→ inhibitory, dampens amygdala activity and weakens emotional reactivity
→ target for anxiety disorders

5-HT1B [cortical]
→ cortical analysis/perception of the world, mood, cognition
→ enables cortical flexibility, antagonists include psychedelics
→ target for depression

Noradrenergic pathways

Major source is locus coeruleus (pons nuclei)

• Optimal baseline activity for cognitive performance

• Primes for stress by activating PFC, ANS, limbic, thalamus, cerebellum

• Large activation decreases attention and memory

• Over-activation seen in panic attacks, PTSD

• Silent in sleep, but high activity in REM
  

Lesion to fusiform gyrus

Impaired facial recognition

Lesion to entorhinal cortex (hippocampal formaiton)

Impaired spatial memory, getting lost

Lesion to amygdala

Impaired recognition and evaluation of facial expressions

Lesion to ventromedial and/or orbitofrontal cortex (of PFC)

Personality changes, becoming aggressive, violent, impulsive

Voluntary cortical vs emotional innervation of the same muscles

Different regulation and control of the same skeletal muscles

• Competition for control of LMNs

• i.e., evolutionary response = freeze, motor system = scream

Motor cortex lesion: voluntary facial expressions only engage one side, genuine amusement shows symmetrical engagement

Emotional region lesion: sufficient/exagerrated voluntary engagement, lopsided emotional engagement

2 core theories of emotion

1. James-Lange Theory [brain reads the body]
   → interpreting physiological changes i.e., injecting adrenaline induces ‘fear’

2. Cannon-Bard Theory [cognition→knowledge→attach meaning]
   → emotional stimuli is analyzed, feeling is triggered, then body responds

Amygdala

Links higher cognition to metabolic responses

• Survival emotions and high activation for fear, rage, sexuality

• Range of sensory (especially olfactory) input

• Learning and remembering emotionally significant events → conditioned fear

• Fast, reflexive emotional responses

• Emotional memories have a high extinction resistance

Major components of the seeking/motivational system

1. Nigrostriatal = habitual, selection, motivation, movement
   SNc (BG) → dorsal striatum

2. Mesolimbic = reward, motivation, reinforcement
   VTA (mesencephalon) → nucleus accumbens

3. Mesocortical = attention, working memory, inhibition, planning
   VTA (mesencephalon) → PFC (humans extends into parietal)

4. Tuberoinfundibular = lactation, motor control, learning, reward, wakefulness
   Arcuate nucleus (hypothalamus) → pituitary gland

Declarative memory

EXPLICIT

• Conscious recollection of facts/events

• Includes semantic memory (facts, GK), episodic memory (personal experiences and events)

• Hippocampus, ACh, Glu, DA

Sensory information
↓
Short-term memory OR Working-memory
↓ consolidation over time ‘held in mind’
Long-term memory Kept through repetition
(hippocampus & medial temporal) (PFC)

Non-declarative memory

IMPLICIT

• Learning and accessing information without conscious awareness

• Expressed typically through action or performance

• Includes procedural memory (skills, habits), priming, classical conditioning

• Cerebellum, amygdala, basal ganglia, DA, NAD, 5-HT

Procedural memory

Type of implicit memory, a motor process in response to a sensory input, acquired via:

1. Non-associative learning: changes in response to a single stimulus like habituation (ignoring), sensitization (intensifying)

2. Classical conditioning (associative learning): forming connections between 2 stimuli/events

3. Priming: prior stimulus exposure influencing subsequent behaviour/responses

Anatomical areas responsible for learning and memory?

Hippocampus New episodic and declarative memories, facts/events

Entorhinal cortex & Memory consolidation, intermediary
parahippocampal gyrus between hippocampus & neocortex

Amygdala Emotional memory, fear-related

Prefrontal cortex Executive function, working memory
(note dorsolateral)

Basal ganglia Procedural memory → habit learning
(note striatum) skills and routines

Cerebellum Procedural learning → motor learning
timing and coordination

Neocortex Long-term memory storage

Structures involved in declarative memory

Sensory information
↓
Cortical association areas (perception, processing, integration)
↓
[MEDIAL TEMPORAL] for LT memory formation
Parahippocampal cortex (contextual/spatial information)
Rhinal cortex (object and multimodal sensory information)
↓
HIPPOCAMPUS (integration into memory experiences + consolidation, episodic memories)
↓
Thalamus (relay between hippocampus and PFC, attention/awareness in encoding & retrieval)
↕
PREFRONTAL CORTEX (strategic retrieval, decision-making, organizing, contextualizing, evaluation)
↓
Cortical storage (distribution theory: other neurons can compensate and still encode in cases of death)

Trisynaptic circuit

For encoding and processing episodic and spatial memory, located in hippocampus

[synapse 1] Entorhinal cortex [interface from PFC, input to hippocampus]
↓ _{perforant path}

[synapse 2] Dentate gyrus [granule cells, axon outputs called mossy fibres]
↓ _{mossy fibres}

CA3 region [pyramidal neurons with 2 main outputs]

(1) Fornix [axon output tract] → leaves hippocampus

(2) [synapse 3] Schaffer collateral fibres [S3] → output to CA1
↓
CA1 pyramidal neurons [input from CA3, output to subiculum and
entorhinal]

Grid cells vs place cells

Both involved in episodic memory (navigating environments, remembering routes, spatial memory)

GRID → create a space metric

• Found in medial entorhinal cortex

• Fire in hexagonal grid pattern as one moves through space

• ‘Coordinate system’ for spatial navigation

• Measuring distance and direction, internal GPS
  

PLACE → use the space metric to anchor specific locations

• Found in hippocampus

• Fire when in a specific location in an environment

• Each cell is tuned to a particular location

• Creates a cognitive map, changing activity pattern

Long term potentiation (LTP) hypothesis

A long-lasting increase in synaptic strength due to

• High-frequency stimulation of a synapse, both pre and post synaptic neurons

• Strong NMDA receptor activation

• Glu released in high activity causing upregulation of receptors and protein structural changes

• Can reinforce circuits so that spatial summation of neuronal input is no longer as essential to fire APs

Cellular-molecular processes that drive LTP in the hippocampus

Glu release
↓_{From presynaptic during high activity}

Activation of AMPA receptors
↓_{Na+ enters causing depolarization on postsynaptic}
NMDA receptor activation
↓ _{Removes Mg2+ block so that Glu can bind}
Ca²⁺ enters signaling pathways
↓_{Triggers signalling via intracellular kinases}

Synapse signalling is strengthened
↓_{More AMPA inserted into membrane allowing stronger response to future signals}

Long term: CREB activation* → new proteins → structural changes

The persistence of LTP depends on whether cyclic AMP response element binding protein (CREB) activates protein synthesis
= plasticity in engram networks

Engrams

A network of neurons and synaptic changes, indicating a memory

• Stored across varying brain regions

• Formed by experience-driven synaptic plasticity (2 types)

  • Long-term potentiation (↑ synaptic strength

  • Long-term depression (↓ synaptic strength)

• Reactivated during recall aka a ‘memory trace’

• Involves dendritic spines

  • The post-synaptic density

  • Rapidly modifiable skeleton of actin filaments + concentrations of glu receptors

  • Highly motile & plastic, form rapidly during STM

  • Repeated circuit activation stabilizes the spine (regulated by CREB)

Learning vs memory

Acquisition of new knowledge or skills, the process

VS

Retention of learned information (both declarative and non-declarative)

Retrograde vs anterograde amnesia

RETROGRADE: inability to recall past memories, typically close to pre-trauma period. Can form LT memories post trauma and long before trauma.

ANTEROGRADE: inability to form long-term memories post-trauma

Working memory

Separate, short-term memory system interacting with both declarative and non-declarative systems to GUIDE IMMEDIATE RESPONSES

• Delay or ‘buffer’ of information for several seconds to elicit response

• Uses frontal and prefrontal cortices to retain courses of behaviour (mistake learning)

• Can be converted to LT storage if via short-term memory

• Can be strengthened to increase capacity

• Indicated by delay activity, sustained neural activity after stimulus is removed, but before response

  • Neurons actively firing to hold information

  • Pattern of delay activity differs by stimulus and function

i.e., delayed match-to-sample task (DMS)
Presented a cue (face) which disappears causing certain PFC neurons to sustain fire to encode the face. Post-delay a new cue appears, and different PFC neurons fire deciding if it matches.

Standard model vs multiple trace theory of memory consolidation

1. Standard model
   → hippocampus only initially forms & consolidates, neocortex is for long-term storage

2. Multiple trace theory
   → hippocampus involved in retrieving all episodic memories (semantics are most likely to become independent over time)