Divided attention
CIRCADIAN RHYTHMS
3 main properties: 1- 24h period. 2- Endogenous (rhythmic responses continue even in absence of stimulation) 3- Entrainable (rhythms can be reset/adjusted by exposure to external stimuli)
Study: rat has access to running wheel -> turns of wheel recorded on chart recorder, plots each wheel rotation as tick on chart -> each line represents one day’s activity -> activity plotted for month under no light 6am-6pm, rat shown to be active during dark hours of day-night cycle
Zetigebers: entrain biorhythms of animals (env time cues) -> light resets the circadian clock
Aschoff & Weber: when isolated from sun, people’s free running rhythms slightly longer than 24h -> go to bed later until sleep cycle reversed
light sensor -> clock -> output pathway
2 parts of SCN: core (light-responsive) + shell (rhythmicity)
Melatonin pathway: Retinal ganglion cells project to visual and non-image forming areas -> Melanopsin RGCs excited by light, project to SCN -> release GABA to pineal gland -> no melatonin release. If dark: SCN release glutamate, pineal gland synthesize melatonin from tryptophan
SCN neurons keep time using clock genes -> clock genes transcribed + translated -> proteins send feedback by interacting with transcription factors, causing ↓ expression -> ↓ transcription = less protein production = less gene expression inhibition = cycle starts anew
Concentration of BMAL1 and 3 Period proteins cycle in counterphase + PER 2 positive regulator of BMAL1 loop + CRY negative regulator of period and cyroptochrome loops
SCN Mechanisms: light info from eye photoreceptors entrains SCN pacemaker -> has a rhythm that drives slave oscillators -> slave oscillators control rhythmic occurrence of 1 behaviour each
MEMORY AND AMNESIA
2 Major memory types: 1- Declarative (conscious). 2- Nondeclarative (procedural memory, unconscious)
Procedural memory: learning motor response in reaction to sensory input. Non-associative: change in behavioural response that occurs over time in response to single stimulus (habituation + sensitization). Associative learning: behaviour altered by formation of associations between events (Classical + Instrumental conditioning)
PFC involved in working memory -> lesions disrupt performance on working mem tasks
delayed response task in monkeys: some neurons responded while animal saw food and unresponsive during delay interval, others fired only during delay interval (could be related to info retention to make correct choice after delay)
Lateral intraparietal cortex (Area LIP): in intraparietal sulcus; involved in guiding eye movements, electrical stimulation elicits eye saccades to specific regions of visual field; Area LIP responses involved in working memory; LIP neurons fire in response to visual cue but maintain firing throughout delay period
Delayed-saccade task: monkeys trained to fix gaze on computer, target shown in periphery of screen, briefly flashed then delay period, at end of delay fixation point disappears, eyes move to remembered spot; activity of neurons stayed high when stimulus removed
Engram: memory trace, location of memory
Mass action principle: all cortical areas contribute equally to learning/memory
Cell assembly: group of simultaneously active neurons; reciprocally connected; internal representation of object held in working memory; if activity reverberated through cell assembly, consolidation would occur if threshold crossed -> growth process strengthen reciprocal connections; whole cell assembly active if fraction of neurons in assembly activated
Hebb taught us: 1- engrams widely distributed Amon connections that link cells of assembly. 2- Engrams involve dame neurons involved in sensation and perception
Medial temporal lobe: hippocampus, Entorhinal cortex, Perirhinal cortex, Parahippocampal cortex; plays role in memory storage
sensory info -> cortical association areas -> parahippocampal and rhinal cortical areas -> hippocampus (fornix) -> thalamus, hypothalamus
Hippocampus: binds sensory info for consolidation; supports spatial memory of location of objects of behavioural importance; involved in storage of memories for length of time
Morris Water Maze: Rats with bilateral hippocampus lesions can’t remember location of hidden platform relative to cues in room; hip neurons selectively respond when rat in particular location in env
Place cells: each neuron in hip has place field, specific locat will evoke greatest response in cell; depend on visual input to determine locat; hip cells preferentially use visual cues to determine location, but in absence of visual cues respond based on other info
Hip place cells study in humans: patients explored then asked to move through virtual env from starting point to finish line; Condition 1: arrows in town pointed correct direction; Condition 2: no arrows, patients navigate based on spatial memory
Grid cells in entorhinal cortex: spatially selective; respond when animal at multiple locations forming hexagonal grid; cells differ in spacing between hotspots in grid, sensitivity for each cell tiles env rodent is in; organized topographically, size and distance bw increased from dorsal to ventral; universal spatial map
Entorhinal cortex: provides input to hip; place fields in hip place cells may result from summation of inputs from grid cells; single place field of hip neuron would be at location where grid locations of multiple input grid cells align
Standard model of mem consolid: info comes through neocortical areas associated w sensory systems -> info sent to medial temporal lobe for processing -> hippocampal system
Synaptic consolid: process by which changes in synapses create memory trace
Systems consolidation: engrams moved gradually over time into distributed areas of neocortex; permanent engrams sorted in variety of regions; before systems consolid, mem retrieval requires hip; after, mem retrieval doesn’t need hip
Multiple trace model of consolid: hip damage can disrupt episodic mem extending back lifetime, so engrams never fully in neocortex; allows for retrograde amnesia resulting from hip damage to sometimes be graded in time, when episodic meme retrieved they occur in dif context from orig experience, recalled info combine w new sensory input, forms new mem trace w both hip and neoc
dStriatum: major component of basal ganglia; inputs from frontal and parietal cortex; output to subthalamic nuclei;; control of voluntary movement; habit learning; lesions result in procedural mem deficits
Radial arm maze: Condition 1- some arms baited w food, others not; rat learns to move through maze efficiently; retrieves food from baited arm, doesn’t enter no food arms; performance depends on memory of baited arms and which arms previously visited (declarative); affected by hip lesions. Condition 2- small lights above arms containing food, unlit arms no food; lights turned on off any time; optimal performance animals return to it arms, avoid unlit arms (procedural mem); rats rely entirely on association between light and food, don’t have to remember previously visited arms; affected by striatum lesions
LEARNING
Memory acquisition/consolidation: Acquisition = initial physical brain changes from sensory input; STM persists without conscious effort. Consolidation = stabilization/storage of some experiences as LTM.
Cellular signature of memory: Area IT = ventral stream, visual recognition. Repeated stimulus exposure -> neurons become more selective + responses more stable -> suggests memory trace.
Distributed memory: Memory not in 1 neuron; stored as pattern of activity across many neurons. Learning changes synaptic weights -> unique network activity pattern for each memory. More neurons = more storage + less effect of damage. Graceful degradation = memories blend/fade gradually with neuron loss.
Hippocampus: Main parts = dentate gyrus + Ammon’s horn (CA1-CA4). Major input = entorhinal ctx via perforant path to dentate gyrus. Trisynaptic circuit: entorhinal ctx -> dentate gyrus (perforant path); dentate gyrus -> CA3 (mossy fibers); CA3 -> CA1 (Schaffer collaterals).
LTP: LTP = long-lasting increase in synaptic strength; first discovered in CA1 HPC; shows input specificity and can last long time. Requirements: synapse active while postsynaptic cell strongly depol; need temporal summation + spatial summation. Cooperativity = multiple synapses must work together to depol postsynaptic cell enough for LTP. Basis for association = co-active inputs get strengthened together.
LTP mechanism: Excitatory synapses use glutamate. AMPA: Na+ influx -> EPSP. NMDA: Ca2+ influx only if glutamate bound + postsynaptic depol removes Mg2+ block. Increase in [Ca2+]i = induction of LTP. Ca2+ activates PKC + CaMKII -> phosphorylate AMPARs (increase conductance) + insert new AMPARs into postsyn membrane -> stronger synapse.
LTD: LTD = long-lasting decrease in synaptic strength. Seen after low-freq stim (1-5 Hz) of Schaffer collaterals. Syn activity + strong depol -> LTP; syn activity + weak/mod depol -> LTD. BCM theory: extension of Hebb; synapses strengthen when correlated activity produces enough depol, weaken when active during only weak depol; explains bidirectional plasticity.
LTD mechanism: Weak depol -> partial NMDA activation -> low Ca2+ influx -> protein phosphatases activated -> AMPARs dephosphorylated + internalized -> weaker synapse. Summary: high Ca2+ -> kinases -> AMPAR phosphorylation/insertion -> LTP; low Ca2+ -> phosphatases -> AMPAR dephosphorylation/internalization -> LTD.
AMPAR trafficking: AMPARs constantly replaced even without stimulation (~50% every 15 min). LTP/LTD shift balance of AMPAR expression at synapse. Scaffold/PSD-95: synaptic capacity depends on scaffold size. PSD-95 = scaffold basis. LTP -> increased scaffold size, increased PSD-95, more AMPAR slots. LTD -> decreased scaffold size, decreased PSD-95, AMPAR removal. LTP especially increases GluR1-containing AMPARs.
Evidence linking LTP/LTD to memory: Inhibitory avoidance learning activates HPC; learning associated with LTP in HPC circuitry; blocking NMDARs during learning disrupts LTP + memory -> strong evidence LTP/LTD involved in mem form
Synaptic homeostasis / metaplasticity: Need limits or synapses would strengthen/weaken indefinitely. Synaptic modification threshold = level of NMDAR activation where no change occurs. After lots of LTP, threshold shifts so more LTP is harder; after lots of LTD, threshold shifts so LTD is harder and LTP easier. Metaplasticity = plasticity depends on prior synaptic/cellular activit
NMDAR subunits: NMDAR = 2 NR1 + 2 NR2 subunits. More NR2B -> favors LTP. More NR2A -> favors LTD. High cortical activity: increased NR2A, decreased NR2B -> favors LTD. Low cortical activity: increased NR2B, decreased NR2A -> favors LTP.
Synaptic scaling: Memories stored as relative pattern of synaptic weights. Absolute strength can go up/down while relative differences stay same. Neuron scales all synaptic weights by same factor. Preserves stored memory patterns. Likely involves CaMKIV + cell-wide insertion/removal of AMPARs/NMDARs.
Memory consolidation: Early synaptic changes are unstable because phosphorylation is reversible and proteins turn over. Long-term memory needs more permanent molecular changes.
CaMKII and molecular switch hypothesis: Ca2+ -> CaMKII activation -> LTP. CaMKII can stay active longer than Ca2+ signal. CaMKII subunits autophosphorylate each other; if activation strong enough, autophosphorylation > dephosphorylation -> persistent CaMKII activity may maintain potentiation. This = molecular switch hypothesis.
Synaptic tagging + capture: Protein synthesis required for LTM. Blocking protein synthesis after strong tetanus: initial LTP still induced but fades in hours. Blocking protein synthesis before learning: animal won’t remember next day. Weak stim can tag synapse. Strong stim elsewhere triggers new protein synthesis. Tagged synapse can capture those proteins. Tag lasts ~2 hrs.
CREB: CREB = transcription factor for protein synthesis needed in LTP/LTM. Binds CRE sites. CREB-2 represses gene expression. CREB-1 activates transcription only when phosphorylated by PKA. Evidence from Drosophila + Aplysia: increased CREB-2 blocks consolidation; increased CREB-1 increases learning efficiency.
ATTENTION
Resting brain / DMN: Resting brain is not inactive; PET/fMRI show substantial activity at rest. DMN regions = mPFC, PCC, hippocampus, lateral temporal ctx. DMN is active when not engaged in overt task and is deactivated during many cognitive tasks.
DMN function: Sentinel hypothesis = broad monitoring of environment even at rest; PCC may monitor visual fields, evolutionary lookout function. Internal mentation hypothesis = supports daydreaming, remembering past/future events, autobiographical memory. Sentinel + internal mentation = high DMN activity; focused sensory processing = low DMN activity.
Selective attention:
Ability to direct attention to chosen objects/stimuli; selective processing of sensory input; allocation of neural resources to info needed at the moment. Classic example = cocktail party effect.
Bottom-up vs top-down attention: Bottom-up (exogenous) = stimulus captures attention without cognitive input. Top-down (endogenous) = attention deliberately directed according to behavioral goals. Late-selection model = filtering occurs relatively late in processing; high-level processing occurs first, then relevance determines what enters consciousness/behavior; explains why personally relevant info like your name can break through.
Overt vs covert attention: Overt attention = orient head/eyes toward stimulus to improve perception, focus image of interest onto fovea. Covert attention = shift attention without moving eyes/head; “corner of your eye.” Both enhance processing at attended location.
Effects of attention: Shifting attention enhances visual sensitivity and speeds reaction time. Valid cues improve detection and RT; invalid cues worsen them. Spotlight of attention = attention moves to illuminate behaviorally important objects/locations and is associated with changes in brain activity.
Physiology of spatial attention: With eyes fixed, shifting attention to different visual field locations changes activity in retinotopically appropriate visual cortex; as attended sector moves away from fovea, activity shifts farther from occipital pole. Shows attention can move independently of eye position.
Feature-based attention: Attention is not only about location. Top-down attention can be directed to visual features like color, shape, speed, motion direction. Selective attention = attend 1 feature; divided attention = attend multiple features. Different cortical areas are recruited for different attended features. Ventromedial occipital ctx linked to color/shape; parietal ctx linked to direction/speed of motion away from fovea.
General attention principle: Many brain regions are involved in attention, and different tasks recruit different attention circuits. Strong overlap exists btw attention circuits and circuits controlling head/eye movements; attention systems may have evolved from orienting systems.
Hemispatial neglect: Unilateral attentional deficit; patients ignore objects/people/their own body on one side of space contralateral to lesion. Problem is attentional, not sensory. Most common after right posterior parietal cortex damage; can also occur with prefrontal/cingulate damage. Less common after left hemisphere damage.
Neglect mechanism: Posterior parietal ctx important for shifting attention to different positions in space. Neglect patients can often still see left-side stimuli but fail to notice/orient to them. Main issues = inability to switch attention, right visual field stimuli capture attention too strongly, difficulty disengaging attention.
Pulvinar nucleus: Thalamic pulvinar responds more when stimulus in receptive field vs when attention elsewhere. Has reciprocal connections with visual cortical areas in occipital, parietal, temporal lobes; modulates widespread cortical activity. Shows synchronous activity with V4 and IT; helps regulate info flow in visual cortex.
Pulvinar lesion effects: Lesions cause abnormally slow responses to contralateral visual stimuli, especially when competing ipsilateral stimuli are present; reduced ability to focus attention contralaterally. Bicuculline in pulvinar facilitates shifting attention to contralateral side.
Frontal eye fields (FEF): Connected to V2, V3, V4, parietal ctx. FEF neurons have motor fields that guide eye movements to specific visual locations. Stimulation causes saccades to neuron’s motor field. Lesions impair initiation of eye movements to contralateral targets and attention to them.
FEF and attention: Activating FEF neurons increases attention within corresponding motor field but not outside it. FEF can boost attention to one location while drawing it away from others; involved in location-specific attention, task switching, ignoring irrelevant info. Likely signals future saccade location to connected cortical areas, enhancing their activity and contributing to physiological + behavioral effects of attention.
LIP: Lateral intraparietal cortex in posterior parietal ctx constructs priority maps using both bottom-up salience and top-down goals. Priority map = representation of where attention should be directed based on conspicuous stimuli + cognitive relevance. LIP also helps direct eye movements and attention; lesions linked to neglect syndrome.
Frontoparietal attention network: Attention emerges from frontal + parietal systems interacting with visual cortex. Bottom-up attention: visual input reaches LIP -> LIP builds salience map -> FEF also represents salience -> feedback to visual areas and eye movement structures enhances processing and brings eyes to foveate salient object. Top-down attention: frontal lobe critical for goals/control; sequence = frontal lobe (PFC + FEF) -> LIP, V4, MT/V5, V2, V1. Goals established in frontal/parietal areas, LIP + FEF create priority maps, visual cortical modulation enhances selected objects.
Consciousness: After sensory info is processed and filtered by attention, next step is conscious awareness. Materialists = consciousness arises from physical neural processes. Dualists = mind/body are different, so consciousness cannot be fully explained physically.
NCC: Koch and Crick defined neural correlates of consciousness (NCC) as the minimal neuronal events sufficient for a specific conscious percept. Goal = identify what neural processing differs when we are aware vs unaware of something.
Studying NCC: Bi-stable images and binocular rivalry are used to study changing conscious percepts while stimulus input stays constant. These paradigms let researchers map neural activity that changes when perception shifts in and out of awareness.
Binocular rivalry: Each eye sees a different image; conscious percept alternates between them. Brain imaging/electrophys can track what change in the brain when consci content switches
Early vs high-level visual areas in awareness: Earliest visual cortical stages do not show a clear hallmark of visual awareness. Correlation between neural activity and awareness increases as recordings move away from V1 along ventral stream toward temporal lobe. Low-level areas like V1/V2 can be active whether or not stimulus is consciously perceived.
IT and consciousness: Inferotemporal cortex (IT), a high-level vision area, is strongly implicated in awareness during binocular rivalry. In rivalry experiments, IT neuron activity fluctuates in sync with the monkey’s reported percept even though stimulus is constant. Neural-perceptual correspondence is rare in V1/V2 but almost universal in IT. Thus IT is more likely part of the NCC for visual awarenes than early visual cortex.
Frontal/parietal cortex and awareness: Human neuroimaging shows perceptual changes in binocular rivalry associated with frontal and parietal cortical activity; activity is time-locked to reported perceptual switches. “Pop-out” of vis stim also linked to frontal/parietal activity, and TMS disrupti of these regions disturbs perception.
Object-specific NCCs: Consciousness may be object/context specific. FFA responds preferentially to faces. PPA responds preferentially to houses/places. During rivalry, house-to-face transition = PPA activity down, FFA activity up; face-to-house = FFA down, PPA up. So activity in FFA/PPA may be NCCs for conscious perception of faces/houses.