Lec 1/ TB Ch 1, 2

Question 1

• Reticulum theory
• Cajal
  
  • silver nitrate method
  • 4 main discoveries
• Brainbow method
• The Brain Observatory
• # neurons in brain
• # neurons in cerebral cortex

Answer 1

• Reticulum theory: all brain cells are fused together to form a big net or reticulum; this unit works in a holistic way
• Cajal:
  
  • silver nitrate method: stain and drew what he saw from the microscope
    
    • Camillo Golgi invented the silver nitrate method
• Santiago Cajal made 4 main discoveries
  
  • 1. Neurons only connect in a specific place called synapse
  • 2. Neurons are connected in principled (based on a set of rules), not randomly
  • 3. Electrical signals travel through neurons in only 1 direction; this allows systematic info flow thru circuits
  • (#4) neurons are independent units that are not joint together
• Golgi supports the reticulum theory; against Cajal’s
• Brainbow method: derived florescent proteins from glowing jellyfish to label specific neurons
  
  • It has 150+ colors
  • Cons: the color labelling is random
  • Current rs: try to tag different types of neurons w/ diff ranges of colors
    
    • Ex. red + orange for neuron type 1
    • Ex. Yellow + green for neuron type 2
    • Ex. Blue + purple for neuron type 3
• Researchers attempt to disseminate results to broad audience
  
  • The Brain Observatory/ The brain’s Hubble telescope
    
    • Constructed the “Concise Digital Atlas of the Human Brain”
    • Ppl can inspect stained sections of the brain at various magnifications (ex. birds eye view of all structures, individual neurons)
• Brains has 100 billion neurons, can stretch for 150,000 km
• Cerebral cortex: 30 billion neurons, 1 million billion connections

Question 2

• LABEL THE DIAGRAM
• Neuron fx
• what are the fx of the following parts?
  
  • dendrites
  • axon
  • myeline sheath
  • nodes of ranvier
  • terminal buttons
  • synapse
• Size of neuron in the retina?
• Length of neuron spinal cord to toes?
• 6 shapes of neurons
• von Economo neurons
  
  • 2 places it is found
  • 7 fxs
  • Who has impaired von Economo neurons?
  • What animals have von Economo neurons?

Answer 2

Anatomy

• Neurons’ function: signal transmission
• Nucleus: Central region
• Neurons look like trees: branching roots, long trunk, bushy crown
• Dendrites: (tree in Greek) Branching roots, receive signals
• Axon: (axle in Greek) long trunk, transmit signals
• Myelin sheath: fat that give insulation to protect and accelerate signals
  
  • 1 mm long
• Nodes of Ranvier: small spaces that separate the Myelin Sheath, rejuvenate (restore energy) the signals
• Terminal buttons: the axon splits into segments, and it ends with the buttons, the buttons relay info to downstream neurons
• Synapses: (syn = together; haptein = to clasp) tiny clefts b/w terminal buttons of message sending neurons and dendrites of message receiving neurons
• Neurons vary in size and shape
  
  • Size: Neurons in the middle layer of the retina: 1 mm
    
    • Neurons that extend from spinal cord to toes: 1 m
  • Shapes: pyramidal, granular, stellate, chandelier, basket, fork
• Some neurons are specialized for certain sensory or motor processing
• Ex. von Economo neurons – found in a few brain regions (anterior cingulate, anterior insula); related to emotional processing, self-awareness, and social cog, interoception (can sense one’s internal bodily’s state), affect and communication in relationships
  
  • Those w/ mental disorders that impair mental capacities (ex. autism and schizo) have altered von Economo neurons
  • Socially complex mammals have many von Economo neurons (apes, elephants, whales, dolphins)

Question 3

• LABEL THE DIAGRAM
• Process of how e- signals are conducted (3 steps)
• Active conduction

Answer 3

Physiology

• 1. Dendrites receives many inputs (in the form of e current) from other neurons
• 2. E current moves to the cell body via passive conduction
     * Passive conduction: passive flow for e current from dendrite to cell body
• 3. Current reaches the base (aka hillock of Axon hillock); if the total sum of the current exceeds the specific threshold, the neuron fires an action potential via active conduction
     * Action potential: aka spike, the neuron experience change in electrical property, this causes the net charge in the axon shift from -ve to +ve
     * Active conduction: reoccurring APs/spikes at the nodes of Ranvier, this allows the signal to travel along the axon w/o fading

Question 4

Physiology cont

• LABEL THE DIAGRAM
• RMP?
• Critical Threshold?
• Process of AP: 3 steps
• Fx of hyperpolarization
• Signal speed of myelinated vs unmyelinated neuron
• Fx of Nodes of Ranvier
• Active conduction
• Process to send signal across synapse
• Summation effect
• % of oxygenated blood used by brain
• Size of arteries, arterioles, capillaries

Answer 4

• By default, the neuron is more -ve in the inside (RMP: -70 mV)
• When the input is +ve enough to increase the MP to -50 mV (aka critical threshold), this triggers an AP (happens in 1 ms)
  
  • 1. Na+ channels open; Na+ enters cell; cell depolarizes, the cell becomes more +ve than the external env
  • 2. Na+ channels close; K+ channels open (slowly K = couch potato); K+ leaves the cell; the cell becomes more -ve
  • 3. Since K+ channels close very slowly, the cell becomes hyperpolarized
       * Hyperpolarization: prevents another AP happen right away; ensures the signal travels forward, not backwards
• Myelin Sheath: increase the speed an axon can transmit current
  
  • Unmyelinated: signal travels 1 m/s
  • Myelinated: signal travels 10 to 100 m/s
• Nodes of Ranvier: small spaces b/w myeline sheaths; renews the AP perpetually
• Active conduction: the cycle of Na+ influx and K+ outflow happens in each node; active conductions is the sequential (entire chain of) signal rejuvenation
• Process to send signal across synapse
• 1. When signals reach the terminal buttons, the have to cross the synaptic cleft (20 nm)
• 2. Here, NT are released, and bind to specific receptors on the postsynaptic neuron
     * NT: chemicals that carry the signals across the synaptic cleft
     * If the presynaptic neuron is excitatory, the released NT make the postsynaptic neuron fire
     * If presynaptic neuron is inhibitory, the released NT make the postsynaptic neuron less likely to fire
• Whether the target cell fires depend on the sum of numerous inputs
• NOTE: the strength of individual inhibitory or excitatory connection is adjustable
• • Neuron activity uses a lot of energy
• The human brain is 2-3% of the total body weight, but uses 20% of the oxygenated blood from the heart
• Oxygenated blood from heart enters blood vessel network: arteries (5 millimetre) -> arterioles (30 micrometres) -> capillaries (10 micrometres; a bit wider than 1 RBC)
• Capillaries
  
  • Have thin walls, oxygen can pass be extracted here
• Veins: deoxygenated blood flows from brain to heart

Question 5

• What does neuron’s firing frequency indicate?
• Why?
• Why are assemblies of neurons arranged in multi-layered hierarchies?
• Visual system
  
  • 2 main stages of processing
  • Describe Table detection network
• How can Hierarchical coding networks be bottom-up feedforward?
• How can Hierarchical coding networks have top-down feedback connections?

Answer 5

Representation

• IOW, the neuron’s firing frequency indicates whether the preferred stimulus present
• Neurons are tuned to respond to specific stimulus
• Assemblies of neurons are put in multi-layered hierarchies; this arrangement help them capture complex patterns of info
• • Ex. Visual system - Object recognition
    
    • There are several stages of processing
      
      • Early stages: process elementary features of shape
      • Other stages: process more complex combination of the features
• Ex. Table detection network
  
  • Level 1 (bottom): 1 cell code for “vertical edge”; 1 cell code for “horizontal edge”
  • Level 2: 1 cell code for length; 1 cell code for “corner”, and this cell receives input from the two cells in lv 1
  • Level 3: 1 cell code for legs; 1 cell code for rectangular surface, and it receives input (i.e. corners and lengths) from cells at lv 2
    
    • IOW, the cell can combine feature of corners and lengths to form the more complex “rectangular surface”
  • Level 4: 1 cell receives input from two cells in lv 3
    
    • IOW: this cell combines features of rectangular surface and legs to derive the final object representation – table
• The table detection network resembles the hierarchical coding in the cerebral cortex, and other perceptual systems
• • • Hierarchical coding networks are seen in bottom-up feedforward (use current feedback, and generate solutions for the future) connections
    • As a result, sensory signals can be matched w/ knowledge stored in LTM
• Hierarchical coding networks are also seen in top-down feedback connections
  
  • This allows our internal priorities and predictions to guide our perceptual processes
  • Top-down connections go from central to peripheral brain regions
  • This allows us to reconstruct specific sensorimotor representations w/o external input
  • Ex. in our dreams, we conjure (bring forth) diff sights, sounds, and smells in our imagination

Question 6

• LABEL THE DIAGRAM
• Planes
  
  • Sagittal
  • Coronal
  • Horizontal
• Location of regions
  
  • Rostral (aka ?)
  • Caudal (aka ?)
  • Dorsal (aka?)
  • Ventral (aka ?)
  • Lateral
  • Medial

Answer 6

Navigating the Neural Landscape

• Planes
  
  • Sagittal: section that separates left and right sides of the brain
  • Coronal: separate front from the back
  • Horizontal (aka axial/transverse): separates top from bottom
• Locations of certain regions
  
  • Rostral/anterior: front of the brain (rostral; rooster; beak is in the front)
  • Caudal/posterior: back of the brain
  • Dorsal/superior: top of the brain
  • Ventral/inferior: bottom of the brain (V points down)
  • Lateral: outer left or right side of the brain
  • Medial: midline of the brain

Question 7

• LABEL THE DIAGRAM
• Brainstem
  
  • 3 sections of brainstem
  • 2 things it maintains
  • Damage causes what?
  • Cranial nerves: what they do?
  • Where do cranial nerves the brain?
• Thalamus
  
  • Where is it?
  • 3 fx
  • Which perceptual input does not pass through a specific nucleus in the thalamus?
  • Which nucleus signals from the retina enter?
  • Which nucleus signals from the cochlea?
  • 3 things thalamo-cortical loops facilitate?

Answer 7

• Brainstem
• has 3 main sections: medulla, pons, and midbrain
  
  • The 3 structures help maintain homeostasis and degree of wakefulness
  • Damage to the 3 structures -> coma or death
• The portal (entrance) for cranial nerves
  
  • Cranial nerves receive sensory input from and send motor output to the head + neck
• Thalamus
  
  • The large egg-shape structure on top of the brain stem
  • We have 2 thalamus, 1 for each hemisphere
  • (#3) It has many separate nuclei that direct the traffic in the brain
  • Thalamus is the “gateway to the cortex”,
    
    • 1. it relays info up to the cortex
         * All perceptual input (except smell) pass through a specific nucleus in the thalamus, then enters the appropriate cortical region
         * Ex. signals from the retina enters the lateral geniculate nucleus, then the primary visual cortex
         * Ex. Signals from the cochlea enters the medial geniculate nucleus, then the primary auditory cortex
         * Ex. signals from the basal ganglia, cerebellum, and amygdala enters the thalamic nuclei, then reach their cortical targets
    • 2. Thalamus receives feedback from the cortex
         * Each specific area in the cerebral cortex has bidirectional (2-way) connection w/ a specific part in the thalamus
         * These thalamo-cortical loops facilitate attention, STM, coordination of diff brain regions (ex. mental representations)

Question 8

• LABEL THE DIAGRAM
• Hippocampus location
• Fornix & Mammillary body fx
• 4 steps Memory consolidation process
• Patient HM
  
  • Which part was removed
  • What was the consequence of surgery
    
    • 3 things he can’t remember
    • 2 things he can
• Amygdala location
  
  • 3 fx
  • Patient SM
    
    • 2 things she can’t do
    • 2 other specific fx of amygdala

Answer 8

• Hippocampus
  
  • Aka Giant seahorse in Greek - Looks like a seahorse tail
  • Located in the temporal lobe
  • Fornix (blue box) & mammillary body: crucial to establish LT declarative memory
    
    • LT declarative memory: mem that can be verbally retrieved and reported
      
      • Ex. facts (current president)
      • Ex. autobiographical info (personal life info, where you went to HS)
  • Memory consolidation process
  • 1. hippocampus receives lots of convergent input from cerebral cortex
  • 2. Then it processes the input by registering the spatiotemporal info for related experiences
  • 3. Then, hippocampus retains these complex patterns
  • 4. After some time (ex. years), the hippocampus transfers this info back to the original cortical areas, which is stored semi-permanently in strongly weighted synaptic connections
  • • Ex. Patient HM
      
      • Had amnesia after his medial temporal lobes were surgically removed
      • The medial temporal lobes were removed as a last resort to alleviate epileptic seizures
      • After the surgery, his seizures stopped, but
        
        • he can’t remember anything that happened to him since 16 yo
        • can’t remember simple things: who he had for his last meal, where he lived, own age
        • can’t learn the meanings of new words
      • IOW: this suggests hippocampus is essential for linguistic process
      • However, he has STM and can learn new motor skills
        
        • This suggest these abilities rely on other brain mechanisms
• Amygdala
  
  • Located at the anterior tip of hippocampus
  • means almond in Latin
  • 1 Responsible for emo processing
  • 2 Helps us assess the significance/ value of the stimuli
  • 3 Sensitive to dangerous situations
  • Patient SM
    
    • Her amygdala developed abnormally in both hemispheres
    • 1 So, she cannot recognize fear expressions in other people’s faces
    • 2 She does not feel fear
    • Researchers brought her to haunted house
      
      • She reacted to the monsters by laughing, smiling, and talking to them
      • She scared the monsters too
    • She went through traumatic life events
      
      • She only felt angry and upset, never fearful
  • Amygdala helps promote adaptive b in threatening situations, and perceiving emotional prosodic patterns in speech (aka emotion in speech)

Question 9

• LABEL THE DIAGRAM
• Basal Ganglia location
• 4 main structures in Basal Ganglia
  
  • 2 structures in Striatum
  • Substantia nigra fx
• How the Basal Ganglia works - 3 steps
• 5 fx of basal ganglia
• • Cerebellum location
• % of neurons in the brain in here
• Purkinje neurons
• 3 fx of cerebellum
• If cerebellum is damaged, 3 main cons

Answer 9

• Basal Ganglia
• Basal ganglia: contains several integrated nuclei, located near the thalamus
• Basal Ganglia contains the following structures
  
  • Striatum: includes the Caudate nucleus and Putamen
  • Globus pallidus or pallidum: has a lateral and medial portion
  • Subthalamic nucleus
  • Substantia nigra: located in the midbrain, generates dopamine, projected into the striatum
• How the Basal Ganglia works
  
  • 1. Striatum receives signals from the cerebral cortex; Striatum recognizes. The signals from familiar situations (ex. I walk up to the door of my fav restaurant)
  • 2. Striatum sends this signal to 2 // routes
       * “go” pathway: this pathway implicitly learn what types of actions are adaptive in certain situations (ex. push the door)
       * “no-go” pathway: this pathway learns what types of actions are maladaptive in certain situations (ex. don’t pull the door)
  • 3. The output from these 2 pathways (i.e. recommendations on what to do or not) are sent to the frontal cortex via thalamus for further consideration
• Basal Ganglia is essential for unconscious acquisition, selection, initiation, and cessation (aka habits OR procedural skills) in motor and cog control
  
  • It influences our motor control (ex. Parkinson’s, Huntington’s)
  • It influences our cog control (ex. schizo, OCD)
• IOW: It influences overt b and covert thoughts
• • Cerebellum: located behind the medulla and pons
    
    • Aka little brain in Latin
    • But, it has more than two thirds of all the neurons in the brain
    • Contains Purkinje neurons
      
      • Purkinje neurons have many dendrites, and receive 200k signals from other cells
    • Cerebellum regulates muscle tone, balance, and movement control
    • Damage to cerebellum: leads to loss of balance, jerking/tremoring from arms and hands, impairs articulatory control causing dysarthria (slurred speech)
    • IOW: cerebellum influences movement and cognition

Question 10

• LABEL THE DIAGRAM
• Cerebral cortex
• Cortex in latin = ?
• Size?
• # of neurons?
• # of connections
• Grey matter - location?
• White matter location?
• 5 major lobes
  
  • 4 visible lobes
  • 1 invisible lobe
• Sulci fx
• Central sulcus
• Lateral sulcus/sylvian fissure
• 2 arbitrary lines

Answer 10

The Cerebral Cortex

• Most highly evolved part of human brain
• It takes up 3.5 pieces of letter sized paper; which is crumpled up to fit in the skull
• • The cortex has 30 billion neurons, each neuron contacts 1000 other cells
• Gray matter: refers to the grey neuron cell bodies in the cortex
• White matter: subcortical tissue is white due to myelinated axons

The Major Lobes–—Visible and Hidden

• There are 5 lobes
• 4 visible lobes on the cerebral cortex
  
  • Frontal
  • Parietal
  • Temporal
  • Occipital
• 1 Invisible lobe: Insula
  
  • Insula = island in Latin
• The borders are defined by sulci
• Central sulcus: separates the frontal and parietal lobes
• Lateral sulcus/sylvian fissure: separates the temporal lobes from the frontal + parietal lobes
• An arbitrary line: separates the occipital lobe from the parietal and temporal lobe
  
  • This line connects the parieto-occipital sulcus (dorsal) with the preoccipital notch (aka dent) (located ventrolateral)
• The other arbitrary line is perpendicular to the line above and extends to the end of the sylvian fissure
  
  • This separates the occipital from temporal lobe

Question 11

• LABEL DIAGRAM
• Gyri
• Sulci
• 2 reasons why gyral-sulcal organization is adaptive
• Axon density in Gyri vs sulci
• How do sulci and gyri form?
• shape and size ulci and gyri: env or genetic?

Answer 11

Gyral–Sulcal Organization

• Gyri: bulges
• Sulci: grooves
• This gyral-sulcal organization is adaptive
  
  • 1. It squeezes a lot of surface area into a small space
       * Two thirds of the cortex is in the sulci
  • 2. It reduces the amount of axonal wiring
       * This reduces the distance signals travel
• In humans and other mammals, axons projecting in the gyri are denser than axons projecting in the sulci
• This suggest the gyral-sulcal patterns are caused by stiff axons constantly pushing harder against some regions on the cortical surface (like condom)
• Since the skull is a physical constraint, the pushed regions protrude outward and form gyri; the other regions bend inward to form sulci
• • shape and size of gyri and sulci is mainly genetic
• This is mainly genetically influenced (slightly env influenced)
• Research showed that cortical convolutions are more similar in MZ than DZ twins
• • Diagram structures
• Figure 1.17
  
  • 2 structure in the sylvian fissure on the dorsal surface of temporal lobe (aka supratemporal plane)
  • 1. HG = Heschl’s gyrus (aka transverse gyrus)
  • 2. PT = Planum temporale
  • Both are key for language and speech processing

Question 12

• cytoarchitectonic organization
• cortex thickness
• # of horizontal layers?
  • Layer I, II, III fx
  • Layer IV
  • Layer V
  • Layer VI
• Define vertical columns
  
  • diameter?
  • # of neurons
• Brodmann’s map
  
  • Which area does it map out?
  • # of Brodmann areas?
  • Areas range?
  • Why are some #s omitted?
  • 2 cons?
  • Which BA area is confirmed?
  • Which BA area is challenged?
  • How many distinct areas does each bran hemisphere has in reality?
  • Is Brodmann map a structural or functional map of the brain?

Answer 12

Cytoarchitectonic Organization

• Cytoarchitectonic organization: whether there is packing density, and layers of diff types of cells
• The cortex is 2-4 mm thick
  
  • Has 6 diff layers of cells stacked
  • Each layer of cells differs in morphological and connectional properties
    
    • Layers I, II, III: communicate w/ other cortical areas
    • Layer IV: receives input from thalamus
    • Layer V: sends output to subcortical motor structures
    • Layer VI: sends output to the thalamus
  • These layers are horizontal
  • There are vertical columns
  • Vertical columns: perpendicular to horizontal layers; basic functional units of the cortex
    
    • Each column is 0.4 mm in diameter
    • There are 100 neurons tuned to respond to similar features from the external or internal env
• Scientists tried to make maps of the cortex
• Brodmann’s map
  
  • the lateral and medial view of a human’s LH
  • there are 43 cortical areas OR Brodmann areas (Bas)
  • The areas ranged from 1 to 52
  • Brodmann omitted 12-16 and 48-51 b/c he used these #s for certain areas in other mammals, but he can’t find them in humans
• In 1980s: BAs are often used w/ gyri and sulci labels to refer to specific cortical regions
• It helped interpret fMRI
• BAs weakness
  
  • 1. No info on the boundaries inside the sulci
  • 2. It is based on subjective observations; does not consider individual differences in anatomy
• Modern imaging methods confirmed some BAs
  
  • Ex. BAs 44 and 45 do exist in the FL (BA 44 and 45 are usually collectively referred as the Broca’s area)
• Modern imaging methods challenged some BAs
  
  • Ex. BAs 39 and 40 can be further carved into 7 areas
• Currently, we know that each human brain hemisphere has 150-200 distinct areas
• Main point: we should treat BA as structurally defined regions (rather than functionally)

Question 13

• LABEL DIAGRAM
• Connectional Organization
  
  • What type of axons carry info b/w cortical regions?
  • Corpus callosum - what it does?
    
    • What matter type?
    • How many axons?
  • What do split brain patients help rs study?
  • What are Fasciculi?
  • Arcuate fasciculi fx
    
    • In which hemisphere?
    • which 3 regions does it secure?
    • What are the 3 connecting segments?

Answer 13

Connectional Organization

• Cortical regions do not work in isolation; they work together to carry out complex mental processes (ex. language)
• The signals are carried by axons that flow through white matter (like highways)
• Corpus Callosum (CC): white matter tract w/ 100 million axons that connects the 2 hemispheres
  
  • The biggest and busiest tract
• split-brain patients allow neuroscientists to examine the behavior from each hemisphere
• Fasciculi: white matter tracts that connect diff cortical areas w/in the same hemisphere
• • Arcuate fasciculi: responsible for linguistics
    
    • In LH
    • It has 3 separate branches that undergird (secure) 3 regions
      
      • 1. Broca’s territory: posterior part of inferior frontal gyrus (BA 44 + 45) and adj portions of middle part of frontal gyrus and precentral gyri
      • 2. Wernicke’s territory: Posterior portions of the superior and middle temporal gyri
      • 3. Geschwind’s territory: supramarginal gyrus and angular gyri
    • The long direct segment: links Broca’s w/ Wernicke’s territory
    • Anterior indirect segment: links Broca w/ Geschwind’s territory
    • Posterior indirect segment: links Wernicke w/ Geschwind’s territory

Question 14

Connectional Organization cont

• LABEL THE DIAGRAM
• 3 other language related fasciculi
• Diffusion tractography
• Human connector

Answer 14

• Other language related fasciculi
• Inferior fronto-occipital fasciculus: links inferior frontal area w/ occipital area
• Inferior longitudinal fasciculus: link temporal areas w/ occipital areas
• Uncinate fasciculus: link OBF area w/ anterior temporal areas
• Main point: there are many long distance fibre tracts that tie the cortical regions together
• This allows for producing and understand language
• Diffusion tractography: measures passive movement of water along axons in white matter (uses MRI techniques)
• This allows us to reconstruct the directions of fibre tracts (as seen in Fig 1.21, 1.22)
• Human connectome: a project that maps all the connections in our brain

Question 15

• Sensory, Motor, and Higher-Order Systems
  
  • 3 primary sensory regions
  • Which cortex does visual info enters?
    
    • BA#?
    • Aka?
    • Location - which fissure?
    • Location - which part of which lobe?

Answer 15

Sensory, Motor, and Higher-Order Systems

• Sensory: vision, audition, and somatosensory
• Vision
  
  • Visual info enters the primary visual cortex in the occipital lobe
  • Primary visual cortex, aka BA17, V1, Striate cortex
  • This cortex is located in the calcarine fissure (Calc F), which is on the medial surface of the occipital lobe

Question 16

• Sensory, Motor, and Higher-Order Systems cont 2
  
  • Retinotopic organization
  • 2 separate streams at the anterior edge of occipital lobe

Answer 16

• PVC has retinotopic organization
• Retinotopic organization: preserves the spatial arrangement of signals from the retina
• The PVC projects forward to other occipital areas that are specialized to extract info on specific attributes of visual stimuli (ex. form, color, motion, depth)
• At the anterior edge of the occipital lobe, the flow splits into 2 separate streams
  
  • 1. “what” pathway: extend to ventral temporal lobe, it recognizes objects based on shapes, colors, and textures
  • 2. “where” path: extend to posterior parietal lobe, represent the locations of objects in relation to each other and in relation to the viewer’s body
       * Aka “how” pathway: promotes visuomotor transformations for object-directed actions
       
       • Ex. convert the position of a coffee mug based on the eye-centred coordinates into hand-centred coordinates

As a result, you can reach out and grasp the cup

Question 17

• LABEL THE DIAGRAM
• Sensory, Motor, and Higher-Order Systems cont 3
  
  • Auditory
    
    • Location - gyrus?
    • Location - fissure?
    • Tonotopic organization
    • hemispheric asymmetries
    • Where are complex auditory fx done? - 3 parts
  • Somatosensory
    
    • postcentral gyrus fx
    • BA #s?
    • aka?
    • Define Somatotopic organization
      
      • large cortical areas means what?
    • 3 types of signals it processes
    • What info do signals from tendons provide?
    • 3 areas that do complex processing of somatosensory info?

Answer 17

• Auditory
  
  • Primary auditory cortex is in the Heschl’s gyrus (located in the Sylvain fissure)
  • Primary auditory cortex area has a tonotopic organization
  • Tonotopic organization: cortical columns next to each other respond specifically to sound frequencies that are next to each other
  • PAC has hemispheric asymmetries: left PAC has more input from the right ear and vv
  • Complex auditory functions are done in the Planum temporale (PT), superior temporal gyrus, and middle temporal gyrus
• Somatosensory cortex (aka postcentral gyrus)
  
  • postcentral gyrus (i.e. BA 1,2, and 3): Signals for felt shape and texture of objects, temp, pressure, and pain are first processed here
  • These BAs have diff fx; but are collectively referred to the primary somatosensory cortex (i.e. S1)
  • This region has rich somatotopic organization
  • Somatotopic organization: cortical representation that captures the body layout in a vertical way, upside down
    
    • w/ disproportionately large amounts of cortical territory for the most sensitive parts of the body (i.e. hands, feet, lips, tongue, and genitals)
    • NOTE: there is some discontinuities
      
      • Ex. face area is not next to the neck area; it is below the hand area
      • Ex. Genital area is not next to the upper leg area, but below the food area
  • the primary somatosensory cortex processes singals from the skin, muscles and tendons
  • Signals from the tendons carry proprioceptive info about the relative positions of one’s body parts in space and about the forces acting on them
  • Sophisticated analyses are done by the posterior and inferior parietal lobe, and the insula

Question 18

• Sensory, Motor, and Higher-Order Systems cont 4
  
  • Motor cortex
    
    • aka - gyrus?
    • aka - cortex?
    • aka - BA#?
    • BA# for higher lv motor programming
      
      • what are the 2 areas
      • There fx
    • 2 higher order networks
      
      • Executive/supervisory network fx
        
        • 2 areas it engages
      • Mentalizing network fx
        
        • 3 areas it engages

Answer 18

• Motor cortex (aka precentral gyrus)
  
  • Postcentral gyrus (somatosensory cortex) matches the precentral gyrus (motor cortex)
  • The precentral gyrus is the primary motor cortex; correspond to BA4, aka M1
  • Many higher lv motor programming regions are in BA6
    
    • Premotor cortex is in the lateral BA6
    • Supplementary motor area is in the medial BA6
      
      • Premotor cortex: contributes to externally triggered actions (ex. slam on brakes when you see a red light)
      • Supplementary motor area: contributes to internally triggered actions (ex. I get up and decide to go for a drive)
• Higher-order systems
  
  • They engage other networks in other lobes of the brain
  • There are 6 other cortical areas
  • Talk about 2
    
    • 1. Executive/supervisory network
         * Depends on regions in the lateral PFC (BA 9, 10, 44, 45, and 46) and inferior parietal cortex (BA 39, and 40)
         * They are used in psychologically demanding situations that needs reasoning, planning, troubleshooting, multitasking, overcoming habitual responses, and keeping info in activated state
    • 2. Mentalizing network
         * Supported by medial PFC (BA 9 and 10), posterior cingulate (BA 23 and 31) and temporoparietal junction (intersection of BA 22, 37, and 39)
         * They help in social interaction; it is engaged when one tries to understand the overt b of other people, and covert mental states (ex. beliefs and desires)

Question 19

• taxi drivers has larger ??
• musicians has more ?? matter in what areas?
• phoneticians have more tissue in ??
  
  • what leads to more tissue?
  • Is this nature or nurture?
• phoneticians have more ?? matter in what area?
  
  • How many HG do they have in LH?
  • Is this nature or nurture?
  • What does this suggest

Answer 19

Box 1.1: Born for Phonetics?

• Being an expert is influenced by structural and functional changes in the brain
• Ex. London taxi drivers have larger hippocampus
• Ex. Musicians gave more grey matter in auditory, motor, and visuospatial areas
• Phoneticians (language experts)
• Exp: Golestani et al 2011
  
  • Analysed the neuroanatomy of
    
    • 17 ppl w/ formal training in phonetic transcription
    • 16 controls
  • Results
    
    • 1. Phoneticians had greater SA and volume in the pars opercularis (a part) of the left inferior frontal gyrus
         * Aka the posterior portion of Broca’s area, known for phonological processing
         * The more training the phoneticians had; the more tissue detected in this area
         * This suggests transcriptional experience result in neural plasticity
    • 2. Phoneticians had more grey matter in the Heschl’s gyrus bilaterally (in L and RS
         * They also had a split or duplicated Heschl’s gyrus in the LH
         * Unlike Broca’s area, this area is not influenced by the length of training the phoneticians had
         * This suggests genetic factors are in play
• Since gyri pattern stabilized by 7 yo
• This may make these ppl more likely to be phoneticians or work in areas using detailed auditory processing
• IOW, they are born for phonetics

Question 20

• Which hemisphere does more language processing?
• Broca area
  
  • Location - gyrus?
  • pars ?? and pars ??
• Wernicke
  
  • Location gyrus?
• Arcuate fasciculus

Answer 20

Language-Related Regions: Broca’s Area, Wernicke’s Area, and Beyond

• Neural system for core components of language is located in separate areas
• Human brain has a strong left hemisphere dominance for language
• It has 2 main regions in this network
• • Broca’s area: includes the posterior portion of the inferior frontal gyrus, specifically the pars opercularis (BA 44) ad pars triangularis (BA 45)
• Wernicke’s area: includes the posterior third of the superior temporal gyrus; it extends to the adjacent temporal and parietal regions
• These 2 regions form a simple network
  
  • Broca’s area: represent the “motor images” of words, it is key for speech production
  • Wernicke’s area: rep the “auditory images” of words, it is key for speech perception
  • The 2 regions communicate via the arcuate fasciculus
• Complex linguistic processes are done by cortical areas working together

Question 21

Neuropsychology

• What do rs study in the field to understand the normal system?
• 2 aims of neuropsychology
• 19 C theory of the brain
• equipotential
• How is it disputed?
• 2 types of dissociation
  
  • single dissociation
    
    • 2 alternative explanations
    • 2 solutions
  • double dissociation
  • Describe Ex. Linguistic distinction b/w nouns and verbs for single and double dissociation

Answer 21

• Researchers study patients with brain damage to make new discoveries on the normal system’s design
• Neuropsychology investigations have 2 general aims
  
  • 1. understand the cog architecture of language
  • 2. understand neural architecture

Single and Double Dissociations

• 19C: ppl think brain operates as a unit
  
  • Equipotential: Each part contributes equally to every ability
• If specific parts of the brain is damaged, specific abilities are impaired
  
  • Ex. damage Broca area → impair speech production
• Dissociations are behavioural data
• There are 2 main types
  
  • 1. Single dissociation
       * Patient is given 2 diff tasks and performs sig worse on X than Y
       * This infers that patient’s lesion has selectively disrupt some mental representations or computation that are needed by the poorly done task but not the better done one
       * Cons: this may not be an accurate conclusion; there are multiple explanations
       
       • In some situations, a single dissociation reflects specific mechanisms for 1 of the 2 tasks is disturbed
       • In other cases, this may reflect that the lesion disturbed the general processing resources that are needed for both tasks, and one of them needs more resources
       • Or the affected task may be harder
         * Solution
       • Ensure the tasks are matched on as many variables as possible (show similar accuracies, RT from healthy controls)
       • Double dissociation
  • 2. Double dissociation
       * Patient A does sig worse on task X than on task Y; Patient B does sig worse on task Y than on task X
       * The reduces the likelihood that patient’s performance is due to task difficulty
       * This suggests that each task needs some unique mental structure/operation and can be selectively disrupted
       * And the ability to do accomplish each task is impaired independently of the other
       * Double dissociation provides compelling evidence that the 2 tasks rely somewhat segregated cog mech
  • Ex. Linguistic distinction b/w nouns and verbs
    
    • Method: single dissociation - You gave patient 2-word retrieval tasks
      
      • 1. name pics w/ objects using the most appropriate noun
      • 2. name pics w/ actions using the most appropriate verb
    • Result: he did sig worse on object-naming task than action-naming task
    • Conclusion: You may conclude that his injury has compromised specific mechanisms essential for producing nouns but not verbs
    • May not be true
      
      • If the target nouns in object-naming task is way longer and less frequent than the target verbs in the action-naming task
      • Ex. orangutan vs walk
      • The patient may have more trouble accessing nouns than verbs as the object-naming tasking was more challenging
      • The patient’s injury then exacerbated his sensitive to the difference in difficulty
    • If you matched the 2 sets of target words for length and frequency, and showed most normal ppl produce both kinds of responses w/ similar speed and accuracy -> the evidence here better supports the conclusion
    • A better way is you demonstrate another patient who is tested w/ the same material showed the opposite dissociation
      
      • i.e. did sig worse on the action naming task than object naming task
    • This is a double dissociation
    • You can support the argument that 2 patients’ impairments most likely affect non-overlapping cog mech
    • You can also support that patient A had an impaired mech essential for noun but not verb production; patient B = opp

Question 22

• Neuropsychology cont 2
  
  • Matzig et al 2009
    
    • Methods
    • Results
  • Rapp and Caramazza 2002 - In-depth study of patient KSR
    
    • Method
    • Results
    • 2 explanations
  • Groups and indiv
    
    • Group: pros, 3 cons
    • Syndrome
    • Indiv

Answer 22

• Matzig et al 2009
  
  • 63 patients w/ noun-verb dissociations
  • The diff b/w 2 categories of words = 30%
  • Findings suggest that the 2 abilities (i.e. name objects w/ nouns, name actions w/ verbs) depend on at least partially distinct cog mech that can be selectively disrupted
  • Note: noun-related and verb-related picture naming deficits can b0 due to problems at several different lv of representation and computation
    
    • Ex visual, conceptual, grammatical, and phonological
  • Need more careful investigation
• Rapp and Caramazza 2002
  
  • In-depth study of patient KSR
  • There is double dissociation in KSR who has brain damage
  • There is an interaction b/w v of grammar category and output modality
    
    • Patient had sig more trouble w/ nouns than verbs in oral production BUT more trouble w/ verbs than nouns in written production
  • Method: sentence completion paradigm w/ noun-verb homophones (same word diff meaning)
    
    • 1. Show patient KSR a “carrier sentence” & a pic of the object or action
         * Carrier sentence - Ex. Give me the (fish); I want to (fish)
  • Results: produced spoken nouns less accurately (40%) than spoken verbs (80%)
    
    • Produced written verbs less accurately (50%) than written nouns (90%)
  • • 2 possible explanations
      
      • 1. The meanings of nouns and verbs are segregated w/in the semantic system
           * Although both types of concepts are still intact for KSR, she has 2 impairments
           * 1. Issue with the object concepts/nouns to speech (phonology)
           * 2. Issue with action concepts (verbs) to writing (orthography)
      • 2. The forms of nouns and verbs are separated in the speech and written output. KSR has 2 impairments
           * 1. Can’t form nouns in speech
           * 2. Can’t form verbs in writing
  • Main point: detailed neuropsychological studies uncover fine-grained disorders
• NOTE: Single and double dissociations can apply to other domains in language (not just noun-verb tasks)

Groups and Individuals

• Group studies and individual studies each have their own pros and cons
• Group studies
  
  • Pros: allow rs to test hypothesis on correlations b/w disturbances from particular mental abilities and lesions
    
    • If a deficit reliably results from damaging a specific area, we should conduct group studies with
      
      • patients w/ + w/o impairment
      • patients w/ + w/o injury
  • Cons: limited on how carefully behavioural criteria is defined
    
    • Each patient has individual set of symptoms due to idiosyncratic brain damage
    • Group studies need to clearly specify the type of impairment that affects the behaviour to sort patients
  • Many rs focused on groups of aphasic patients who belong to certain “syndromes”
  • Syndrome: collection of symptoms that tend to co-occur statistically
  • Ex. Broca’s aphasia is a syndrome
    
    • Some Symptoms:
      
      • Can’t produce complex sentences
      • Worse retrieval of verbs than nouns
      • Poor articulations
  • Most rs treat patients as similar in their studies
  • Caramazza et al think this is invalid
    
    • These patients do not have all the same symptoms
    • They think syndromes like Broca’s aphasia lack empirical and theoretical use
  • Some think we should sort patients based on presence or absence of particular symptoms
  • Issue: symptoms like “worse retrieval of nouns than verbs in picture naming tasks” can have several different causes (see Rapp and Caramazza 2002 abv)
• Individual studies
  
  • Provide insight on how the mind/brain is organized
  • Ex. Patient HM in Ch 1 helped rs develop theories on the role of hippocampus for LTM, and amygdala for emo processing

Question 23

• Neuropsychology cont 3
• MRI Basic mechanism
  
  • Brain is mainly made of?
  • 4 steps
  • Why can we see different type of organic tissues?

Answer 23

Visualizing the Brain: The Basic Mechanics of Magnetic Resonance Imaging

• First technique: computed axial tomography (CAT/ CT)
• Common technique: MRI
• Obtains structural images of the brain in vivo
• MRI Basic mechanism
  
  • Brain consists mainly of water; Each water molecule has 2 H atoms, and their protons are constantly spinning
  • This creates many tiny magnetic fields
  • 1. Normally, the orientation of the magnetic fields is random
  • 2. MRI machine changes the orientation by applying a strong magnetic field (1-10T) on the water molecules which are affected by gravity’s magnetic field (0.001 T). As a result, the protons align with this magnetic field.
       * Higher T/magnetic field, higher resolution
  • 3. Apply radio wave; this cause protons to absorb the wave energy and shift 90 deg
  • 4. Once the radio wave is turned off, the protons relax and align back with the external magnetic field. They emit a detectable signal.
  • We can see organic tissues (ex. white and grey matter) b/c they have diff densities of H atoms
  • This allows us to measure the differences in the relaxion rate of protons
    

Question 24

• Neuropsychology cont 4
• Types of brain damage
  
  • Stroke
    
    • Aka
    • what happens?
    • What is the most common type?
      
      • What happens to it?
    • 2 types of ischemia
      
      • differences?
    • What happens if it blocks brainstem?
    • What happens if it blocks white/cortical matter?
    • How to alleviate the deficits?
    • What happens if the deficit is not alleviated
  • Traumatic brain injury
    
    • Age group this is most common in?
    • 2 main types
    • When are they likely to happen?
    • Gabrielle Giffords
  • Neurodegenerative and Infectious Diseases
    
    • How are these diseases different that stroke and TBI?
    • their 2 main targets
    • the 10 disorders related to language (7 affect language in indirect ways; 3 PPA)
      
      • disorder name
      • type
      • affected brain region
    • PPA?
    • voxel-based morphometry (VBM)
      
      • What imaging technique?
      • 2 step process

Answer 24

Types of Brain Damage

• Stroke (aka cerebrovascular accident – CVA)
  
  • Occurs when blood supply to a particular part of the brain is interrupted
  • Common type: ischemia
    
    • Blood vessel in the brain is obstructed by a clot, and this deprives downstream tissue of oxygen
    • Thrombotic ischemic stroke: the clot forms w/in the blood vessel eventually gets clogged
    • Embolic ischemic stroke: clot originates in a diff part of the circulatory system (ex. heart, large vessels of upper neck and chest)
      
      • This travels up to the brain and get stuck in the capillaries
  • If it blocks sectors of the brainstem for basic life functions -> person will lose consciousness and die in minutes
  • If it blocks certain cortical and white matter areas that support specific cog capacities, the person lives but the cog capacities are compromised
    
    • Ex. strokes that block the posterior cerebral artery that supplies to occipital areas -> visual impairments
    • Ex. Strokes that block the middle cerebral artery that supplies to the perisylvian areas for linguistics -> linguistic impairments
  • Deficits can be partially or completely alleviated if blood flow is rapidly restored to the deprived tissue
  • If not, the tissue will die and become absorbed
  • This leaves a cavity that gets filled w/ CSF
• • Traumatic Brain Injury
    * The most frequent form of brain damage suffered by ppl under 40
    * 2 main types
    * 1. Closed head injury
    * Occurs when person sustains a sudden blow to the head that damages the brain and leaves the skull intact
    * Ex. car accidents, sporting events
    * Ex.
    * Superficial damage to left perisylvian territory
    * Patient had aphasia, but not motor or sensory deficits
    * 2. Open head injury
    * Both the brain and the skull are penetrated by an object (ex. bullet, shrapnel)
    * Ex. Gabrielle Giffords
    * Forced to resign from her set in US House of Representatives after being shot in the head on 2011
    * Remains seriously disabled
    
    • Neurodegenerative and Infectious Diseases
      
      • Brain damage from stroke and TBI have immediate effects
      • Neurodegenerative and infectious disease are progressive
      • There are many disorders and all involve gradual atrophy (i.e. tissue loss) in specific regions/sets of regions in the brain
      • These disorders target particular networks that
        
        • Have a strong functional-anatomical connection
        • Are sig correlated to grey matter volume
      • 10 disorders have cons for language (table)
        
        • First 7 affect language in indirect ways
          
          • They impair certain aspects of perception, memory, cognition, and motor control that are necessary for efficient production and comprehending words/sentences
        • Last 3 are PPA
          
          • PPA = primary progressive aphasia
          • PPA target core components of language circuitry
          • Distinctive patterns of slowly worsening language deficits
          • Distinctive patterns of regionally specific atrophy
          • The 3 PPA have nonoverlapping distributions of cortical atrophy
          • 3 types
            
            • Nonfluent/agrammatic variant: tissue loss in left inferior frontal cortex
            • Semantic variant: anterior temp lobe (bilaterally)
            • Logopenic variant: left temperoparietal area
      • voxel-based morphometry (VBM)
        
        • A type of MRI
        • 1. It divides the brain into thousands of voxels (i.e. tiny cubes)
             * Each cube is a volume (similar to pixels)
             * 2. determines concentration of grey and white matter in each voxel
             * Rs can determine the locations and magnitudes of atrophy in patients w/ neurodegenerative/infectious diseases
             * Then compare them to healthy controls

Question 25

• Neuropsychology cont 5
• Tumours
  
  • Definition
  • Glioma: definition
  • Growth rate
  • Kinno et al 2009
    
    • Japanese-speaking patients w/ gliomas affecting Broca’s area
    • Method
    • Results
• Using behavioral data and lesion data
  
  • 3 steps Lesion Overlap and Subtraction Analysis
  • Tranel and Kemmerer 2004 - understand neural basis of impaired knowledge on meanings of location prepositions
    
    • Locative prepositions
    • Part 1
      
      • Methods
        
        • 4 tasks
      • Results
    • Part 2
      
      • Method
      • Results
  • Voxel-Based Lesion–Symptom Mapping (VLSM)
    
    • 3 steps
    • Wu et al 2007 - VLSM & locative prepositions
  • 3 caveats About Neuropsychological Research on Structure–Function Relationships
  • 2 ways where areas are dysfunctional and may not show up on MRI
  • Apraxia of Speech (AOS)
  • Nina Dronkers 1996
    
    • Method
    • Results
    • 3 limitations
  • Argye Hillis 2004
    
    • Methods
    • Results
  • What went “wrong” w/ Dronker’s study?

Answer 25

• Tumours
  
  • Lesions can be due to tumors
  • Tumours: masses of tissue that grow abnormally and serve no physiological purpose
  • Several type (classified based on how they dev, and likelihood to recur after surgical removal)
  • 1. Glioma
       * Come from white matter and expand outward -> destroy or displace neurons
       * Variable rate of growth (can be v slow or fast)
       * Glioma patient studies are useful
       * Kinno et al 2009
       * A group of Japanese-speaking patients w/ gliomas affecting Broca’s area had sig worse comprehension for passive sentences than active ones
       
       • Ex. Passive – Person A is being pushed by Person B
       • Ex. Active – Person A is pushing Person B
       • Original stimuli: Japanese sentences paired w/ scenes with 2 ppl
         * Another study
       • Showed these patients’ lesion sites overlapped w/ an area that was engaged sig more by passive than active sentences based on another fMRI study
       • They compared them to healthy controls who did the same task
         * Since the neuropsychological data and fMRI data aligns, this shows reliable inferences can be drawn from Glioma studies

Relationships Between Behavioral Data and Lesion Data

• -> discuss how groups studies are conducted
• Lesion Overlap and Subtraction Analysis
  
  • 1. Two groups of patients
       * Gp A w/ deficit of interest
       * Gp B do not have it
  • 2. Each groups has separate procedures
       * Reconstruct the patients’ lesions on a standard brain template
       * Calculate how much overlap for every voxel
  • 3. Lesion overlap map for patients w/ deficit minus lesion overlap map for patients w/o deficit -> remaining area = areas of damage that is linked w/ deficit
  • Tranel and Kemmerer 2004
    
    • Tried to identify the neural basis of impaired knowledge on meanings of location prepositions
    • Locative prepositions:
    • Ex. in, on, around, through, above, below
    • Methods
      
      • 4 tasks given to 78 brain-damaged patients (from stroke)
      • 1. Naming (80 items)
           * Ppl are shown objects and are asked to orally name the location of one object relative to another
      • 2. Matching (50 item)
           * Ppl are shown 3 spatial arrays of objects w/ a preposition
           * Told to choose which array best represent the preposition
      • 3. Odd one out (45 items)
           * Ppl are asked to choose which one involves a type of relationship that is different from the other two
      • 4. Verification (44 items)
           * Ppl are shown a spatial array of abstract shapes together and a preposition
           * They need to decide whether the preposition correctly describes the array
           * * Results
      • Very variable: some failed none, some failed one task, some failed all 4 tasks
      • Those who failed all 4 tasks may have impaired knowledge on the location preposition meanings
      • Those who only failed only 1 task had unimpaired knowledge on meanings but may have individual disturbances on certain processes
    • Part 2
      
      • Rs created lesion overlap maps for those w/o impairments; and one for those w/ impairments
      • Then they subtract the maps from each other
      • Result shows defective knowledge on the meanings of location prepositions is associated w/ damage in some areas in LH
        
        • The cortex and underlying white matter in the inferior frontal, inferior parietal, and posterior superior temporal regions (red, orange, yellows)
        • • The analysis includes patents w/ the deficit of interest and those w/o
    • So, the results provide strong evidence that the lesions mentioned are more likely than not to cause the deficit
• Voxel-Based Lesion–Symptom Mapping (VLSM)
  
  • 1. Administer a task to patients w/ various lesions
  • 2. Patients’ lesion sites are transferred to a standard brain template
       * For each voxel, 2 gps of patients are formed:
       
       • Those w/ brain lesions vs those w/o
  • 3. For each voxel, rs do a t-test to compare the behaviour performances of patients in the lesioned and non-lesioned groups
       * The resulting t-values measures the degree on whether decreasing task performance is related to the presence vs absence of certain brain areas being damaged
  • IOW, VLSM allows rs to identify the neural reasons of deficits, quantify brain-behaviour relationships w/o classifying patients based on their impairment
  • Wu et al 2007
    
    • Used VLSM to study impaired knowledge of meaning of location prepositions
    • 14 patients w/ LH lesions
    • They do several tasks the sentence w/ location prepositions w/ 1 of 4 pics
    • Results: accuracy range b/w 43% to 100%’ mean = 86%
    • The lesioned areas are consistent w/ those from Tranel and Kemmerer (2004 – abv)
• A Few Caveats About Neuropsychological Research on Structure–Function Relationships
  
  • 3 caveats
  • 1. To infer a causal relationship b/w an impaired ability and damage to a specific region, need to show that
       * Patients w/ deficit have lesions at that site
       * Patients w/ lesions at that site tend to have the deficit
  • 2. Deficit-lesion correlations for those w/ stroke/TBI in the chronic period can be diff from those in the acute period
       * Chronic period: 6+ mo after lesion onset
       * Acute period: less than 6 mo after lesion onset
       * This is b/c acute patients w/ small lesions recover fast; the intact areas “take over” the affected fx
  • 3. Some impairments may be due to areas that are not structurally damaged
       * These areas are dysfunctional and may not show up on MRI
       * 2 ways
       * A. Hypoperfusion: receives enough blood supply to survive but not enough to operate normally
       * B. Diaschisis: they depend on axon input from the site of structural damage; but the input is no longer available
  • Apraxia of Speech (AOS): disorder of articulatory programming in Broca’s aphasia
    
    • AOS affect high-level motor aspects of orchestrating speech
    • This leads to distorted consonants, vowels, and prosody
    • Patients know what they want to say and how it should sound, but cannot coordinate the articulators (i.e. lips, tongue, jaw, and palate) to produce the output
  • Nina Dronkers 1996
    
    • Showed 25 chronic stroke patients w/ AOS had 100% lesion overlap in one LH region – superior anterior part of the insula
    • 19 chronic stroke patients w/ AOS had that damage
    • 3 limitations (related to 3 caveats above)
      
      • 1. Results show that AOS is associated w/ a damaged area of insula; but it doesn’t tell if damage to that area give rise to AOS
           * It is possible that AOS may also involve damage in other areas
      • 2. All the patients were chronic; acute patients may show diff deficit-lesion correlation
      • 3. The study only focused on structural damage
           * Other areas that are intact but are dysfunctional by contribute to AOS
  • Argye Hillis 2004
    
    • Addressed the 3 limitations in Dronker’s study
    • Methods
      
      • 1. Selected 80 stroke patients based on site of structural damage
           * 40: lesion on any part of the left insula
           * 40: spared that area
      • 2. Patients were eval for AOS when they were acute (24 hr of stroke onset)
      • 3. Patients were scanned of tissue damage, and also areas of hypoperfusion (sig reduced blood flow)
    • Results
      
      • Abnormalities in region of interest (superior anterior part of left insula) is not sig related to AOS
        
        • 12 out of 29 patients (40%) who had damage or hypoperfusion in that area showed AOS
        • 19 out of 51 patients (40%) who did NOT hv damage or hypoperfusion in that area showed AOS
      • AOS is actually associated w/ abnormalities in Broca’s area
        
        • 26/30 (90%) who had damage or hypoperfusion in that area showed AOS
        • 5/50 (10%) who did NOT hv damage or hypoperfusion in that area showed AOS
    • What went “wrong” w/ Dronker’s study?
      
      • The insula is the most vulnerable to stroke due to anatomy
      • Maybe 80% of Dronker’s chronic patients had damage to Broca’s area, while the remaining patients had hypoperfusion in that area

Question 26

Functional Neuroimaging

• aka
• Vampire theory
• Fulton 1930 & Walker who had many congenitally abnormal blood vessels in occipital cortex
• Positron Emission Tomography (PET)
  
  • fx
  • process
  • spatial resolution & temporal resolution

Answer 26

Functional Neuroimaging

• Aka hemodynamic methods (b/c vampire theory)
  
  • PET & fMRI (more common)
  • Map the function in human brain
  • Vampire theory: the more active regions suck more blood
  • Key process
    
    • 1. When the cog task uses a particular brain area, the active neurons in that area rapidly consume the oxygen available in the local capillaries
    • 2. A few seconds later, there is an overabundance of oxygenated blood
• Fulton 1930s
  
  • Dr. Fulton worked w/ Walter who had many congenitally abnormal blood vessels (arteriovenous malformation) in occipital cortex
  • It causes headaches and visual disturbances
  • When blood pass through those vessels intensely, it produces a pulsing sound that the patient hears as a humming sound
  • Dr. Fulton can also hear it when putting a stethoscope at the back of patient’s head
  • Dr. Fulton found that the rushing sound is correlated w/ Walter’s heartbeats and visual experiences
  • Ex. If Walter lied in the dark for a few minutes and suddenly use his eyes OR reading smth attentively, the sounds gets louder
  • This shows that changes in blood flow reflect changes in neural activity in certain regions, and this affect cog changes

Two Techniques

• Positron Emission Tomography (PET)
  
  • Measures regional cerebral blood flow, which infers regional neural activity
  • The machines tracks the distribution of radioactive isotopes throughout the brain
  • 1. Rs create an isotope in a medical cyclotron, and place it in water
  • 2. This radioactive water is sent to the imaging facility, and rs inject it into the subject’s bloodstream. The bloodstream carries the radioactive water into the subject’s brain.
       * 15 O is the most common isotope used
       * It has 8 p+ and 7 n0
       * When it decays, it releases a proton that is +vely charged (i.e. positron)
       * The positron travels and is attracted to surrounding/ambient electron; this causes the electron and positron to be destroyed (annihilated)
       * As a result, 2 photons are released in opposite directions
       * These photons exit the head and are picked up by the rings of detectors in the PET scanner
       * The computer reconstructs the annihilation location in the subject’s brain
       * If there is a large # of annihilation events in an area, this suggests there is more blood flow in that area. This in turn indicates there is more neural activity
  • Spatial resolution: 10mm (kinda bad)
  • Temporal resolution: 30s (bad)
    
    • Reason: need to average the data over the length of time to get a good signal-to-noise ratio??

Question 27

Fx neuroimaging cont 2

• fMRI
  
  • What is it sensitive to?
  • BOLD
  • 12 second hemodynamic response function (4 steps)
  • Is BOLD correlated to input or output processing of neurons
  • Spatial and temporal resolution
  • 3 Pros of fMRI over PET
  • 2 Cons

Answer 27

• Functional Magnetic Resonance Imaging (fMRI)
  
  • Sensitive to degree of oxygenation of blood in diff parts of brain
  • Blood oxygenation level dependent signal (BOLD)
    
    • Endogenous contrast agent: deoxygenated blood reduces the MRI signal; oxygenated blood increases this
    • When hemoglobin is not carrying any oxygen, it behaves like a small magnet and disrupts the local magnetic field
    • This reduces the signal received by the fMRI machine
    • When hemoglobin is carrying oxygen, it is less magnetic
    • The fMRI can still detect them as a small increase in resonance signal
  • 12 second hemodynamic response function
    
    • 1. When neurons in a specific area increase in activity, they consume the oxygen that is immediately available
    • 2. As a result, there is more deoxygenated blood in that area, and the fMRI will pick up a small decrease in BOLD signal for 2s
    • 3. In the next 5s, more oxygenated blood is detected in that area, and the fMRI detects this as a gradual increase in the BOLD signal
    • 4. For the next 5s, the signal will return to baseline and briefly undershoots
  • The BOLD signal maybe more correlated to the input processing of neurons rather than output
  • Spatial resolution: 1-3 mm
  • Temporal resolution 50-100 ms
  • Pros of fMRI over PET
    
    • 1. Cheaper: doesn’t need a medical cyclotron
    • 2. Safer: doesn’t use radioactive isotopes
    • 3. Better spatial and temporal resolution
  • Cons
    
    • 1. It is very noisy
    • 2. BOLD signals are distorted near air-filled cavities
         * It is tricky it get data from some brain regions, esp the anterior temporal lobes located near the sinuses
         * (rs found a way around this)

Question 28

Fx neuroimaging cont 3

• Standardized Three-Dimensional Coordinates for Defining Stereotaxic Brain Space
  
  • Units?
  • What do we do in fMRI studies
  • Origin?
  • x axis plane?
  • y axis plane?
  • z axis plane?
  • 2 diff atlases/3D grids
  • Fedorenko and Kanwisher 2009
    
    • Cons of analysing multiple subjects for fMRI
    • Solution
      
      • 3 steps

Answer 28

Standardized Three-Dimensional Coordinates for Defining Stereotaxic Brain Space

• In fMRI studies, rs transform the anatomic confiscation of each subject to a standard brain template, then they combine data across subjects
• Stat sig activations are identified and reported in the common stereotaxic space of the standard brain template
• The brain template uses the x,y,z coordinate system
• The origin is the anterior commissure
• • X-axis: right-left dimension (right = +ve; left = -ve)
    
    • Y-axis: anterior-posterior (anterior = +ve; posterior = -ve)
    • Z-axis: superior-inferior (superior = +ve; inferior = -ve)
• 2 diff atlases/3D grids (unit: voxels)
  
  • 1. Talairach and Tournous
       * Based on anatomical data from 1 post-mortem brain
  • 2. Montreal neurological institute (MNI) 1994
       * Based on MRI scans from 305 healthy subjects
• They are similar but not identical
• Old studies voxel size: 3-5 mm
• New studies: 1 mm
• Potential cons of analysing multiple subjects for fMRI
  
  • Fedorenko and Kanwisher 2009
    
    • This may obscure indiv diff in neural organization of language by removing anatomical variability b/w ppl’s brains
    • Potential solution: Plot each subject’s unique functional data on his/her anatomical data
      
      • 1. Locate a region of interest (ROI) in each subject
           * Ex. Fusiform Face Area – sensitive to seeing faces
      • 2. Test for other response properties for that ROI
           * Ex. See if FFA is more sensitive to upright vs inverted faces
      • 3. Conduct analyses across subjects using data from corresponding functional regions rather than drawing from the same locations in Talairach/NMI space
    • May provide more insight

Question 29

Fx neuroimaging cont 4

• Blocked Versus Event-Related Designs
• Block design
  
  • When do we use it? (neuroimaging technique)
  • fx
  • How it works
• fMRI study design options
  
  • block design
    
    • 2 differences compared to other techniques when using block design
  • event-related design
    
    • definition
    • how it works
    • 3 pros

Answer 29

Blocked Versus Event-Related Designs

• How should we order individual trials in experimental condition?
• Ex. You want to identify and compare brain regions that respond to words for animals (ex. rabbit) and words for tools (ex. pencil, knife)
• -> How do we sequence the trials for animal words and tool words?
• This depends on the imaging technique
• PET
  
  • Need to use block design b/c PET has poor temporal resolution
  • Block design
    
    • Trials for the same experimental condition are grouped together in blocks
      
      • Here, the subjects must do the same type of task for the same type of stimuli throughout the block
    • Ex. You set up 3 blocks in your PET study (each block = 1 min)
      
      • Block 1: Condition A – ppl read words for animals
      • Block 2: Baseline condition – ppl lie in the scanner; do nothing
      • Block 3: Condition B – ppl read words for tools
    • These blocks are separated by 10 min periods – this is to allow time for the radioactive isotope subjects receive at the beginning of each block to decay
    • Hypothetical results:
      
      • Strongest signal: Block 1/Condition A- read words for animals
      • Weakest signal: Block 2/Baseline – rest
      • In b/w: Block 3/Condition B – read words for tools
    • • fMRI
  • Since it has better temporal resolution, you have more design options (2 options)
  • Option 1: You can use block design, but there will be
    
    • More blocks per condition
    • Shorter blocks (30s)
    • Same hypothetical results:
      
      • Strongest signal: Block 1/Condition A- read words for animals
      • Weakest signal: Block 2/Baseline – rest
      • In b/w: Block 3/Condition B – read words for tools
    • • Option 2: Event-related design
    • The trials belonging to diff experimental conditions are randomly scattered
    • Each trial has its own hemodynamic response
    • These indiv signals are later extracted and averaged based on the condition
    • Same hypothetical results
      
      • Strongest signal: Condition A- read words for animals
      • Weaker singal: Condition B – read words for tools
      • • Why are event-related design popular?
  • 1. Allow rs to randomize stimuli
       * Reduces the chance the results are influenced by habituation, anticipation, or strategic processing (which r more likely in block design)
  • 2. There’s more experimental flexibility than block design
       * Trials can be sorted by diff criteria
       
       • Ex. conditions, uncontrollable factors (trials subjects responded incorrect)
  • 3. Can see more details on amplitudes and time trends of hemodynamic response in diff brain regions

Question 30

Experimental paradigms

• Which study design are experimental paradigms usually used w/?
• Subtraction paradigm
  
  • What study designs can used this paradigm?
  • What neuroimaging methods can use this paradigm?
  • Methods - how to use
  • Narain et al 2003: Aims to disclose brain regions linked w/ auditory processing of intelligible vs unintelligible sentences
  • 4 conditions
  • Methods
  • Final activation map
• Correlation paradigm
  
  • What study designs can used this paradigm?
  • How it works
  • Mobbs et al 2010 - Looked at the neural activity associated w/ monitoring the threat value of a tarantula
    
    • Methods
    • Results
  • Davis and Johnsrude 2003 - Used correlation paradigm to further explain the neural underpinnings of intelligible and unintelligible
    
    • Methods
    • 5 conditions
    • 3 diff degrees of intelligibility
    • Results
      
      • Subtraction paradigm
      • Correlation paradigm
      • Follow up analyses
  • Multivariate Pattern Analysis
    
    • How is it different from subtraction and correlation paradigm?
    • What it does?
    • Mur et al 2009/ Raizada et al 2010
      
      • orthogonal pattern detection
    • Abrams et al 2013 -Used MVPA to examine the neural substrates that process intelligible vs unintelligible utterances w/ better precision
      
      • Methods
      • Analysis
        
        • subtraction
        • MVPA
      • Results

Answer 30

Some Basic Experimental Paradigms

• Subtraction, correlation, and pattern analysis are mainly used w/ event-related design, but occasionally w/ block design
• Subtraction paradigm
  
  • First paradigm used in fx neuroimaging
  • Can be used with blocked and event-related designs
  • Used by fMRI and PET rs
  • Helps rs isolate neural correlates of specific cog capacities
  • • Study design: 2 conditions
      
      • Experimental: ability of interest
      • Baseline/Control: does not include ability of interest, equivalent in other aspects
  • 1. Collect imaging data
  • 2. Map of brain activity w/ experimental condition “-“ map of brain activity w/ control condition
       * The regions that still show up is sig engaged in the experimental condition; this is treated as uniquely contributing to the ability of interest
  • To enhance reliability, we include
    
    • multiple experimental conditions that require the ability of interest (Ex. conditions A and B)
    • multiple control conditions that do not (Ex. C and D)
  • This allows rs to conduct conjunction analyses that increase the likelihood of pinpointing brain regions responsible for the interested ability
  • • Ex. If each experimental condition is well-matched w/ a particular control condition
      
      • Ex. A w/ C, B w/ D
      • 1. Perform separate subtractions b/w corresponding conditions
      • 2. Conjoin outcomes of the independent analyses [(A – C) + (B – D)]
      • The resulting brain map is quite restricted, and helps narrow the neural underpinnings of specific cog capacities
  • Narain et al 2003
    
    • Aims to disclose brain regions linked w/ auditory processing of intelligible vs unintelligible sentences
    • 4 conditions: 2 using intelligible stimuli, 2 using unintelligible stimuli
    • Intelligible conditions
      
      • A. Speech (Sp): normal sentences
      • B. Vocoded speech (VCo): sentences that are artificially altered to have a rough sound quality but still can be understood
    • Unintelligible conditions
      
      • C. Rotated speech (RSp): Sentences that are spectrally rotated (i.e. inverted) so they sound like “alien” language;
        
        • but still have phonetic features (ex. voiceless fricatives – “f”, “th”)
      • D. Rotated vocoded speech (RVCo): Sentences that have been vocoded and spectrally rotated (i.e. inverted) so they sound like intermittent fluctuating static
    • 11 ppl listened to blocks of stimuli from each condition during fMRI scanning
    • All state they can only understand stimuli 2 out of 4 conditions
    • Rs identified the brain regions that mediate extracting meaning from intelligible utterances using the “subtraction” method
      
      • [(A – C) + (B – D)]
      • [(Sp – RSp) + (VCo – RVCo)]
      • 1. Do 2 separate subtractions
           * Each involves contrasting the activation evoked by intelligible stimuli against the matched set of unintelligible stimuli
           * Intelligible and unintelligible conditions differ only by spectral rotation
      • 2. Conjoin (add) activation maps from the 2 separate subtractions; this identifies the commonality
           * This captures brain areas that respond to both intelligible stimuli
           * This rule out areas that respond to only one intelligible stimuli and areas that respond to both unintelligible stimuli
    • Final activation map
      
      • Only 3 clusters of voxels are stat sig
      • They are in the left lateral temporal lobe
      • Some portion overlap with Wernicke’s area,
      • Damage to that area disrupts phonological and lexical aspects of spoken language comprehension
      • It’s possible lateral temporal region contributes to high-level auditory sentence processing, not low-level acoustic and phonetic info
    • Note: analysis was restrictive
• Correlation paradigm (aka parametric paradigm)
  
  • Compatible w/ blocked and event-related design
  • The ability of interest here is a continuous variable that can vary; it is not all-or-nothing
  • Subjects perform a series of tasks that uses the ability of interest in diff extent
    
    • Rs look for brain regions where the activity level changes correspondingly
  • Mobbs et al 2010
    
    • Looked at the neural activity associated w/ monitoring the threat value of a tarantula
    • 1. Ppl were placed in fMRI, one foot is in a box w/ 5 compartments
    • 2. Ppl think they were seeing a live camera feed where a rs move a large tarantula from one box to another, closer/farther from their foot
         * Reality: they are liking at a pre-recorded clip
    • Results from parametric regression analysis
      
      • As the spider got closer to the foot, brain activity increased in anxiety-related areas
        
        • Dorsal anterior cingulate cortex, midbrain nuclei
      • As thee spider got farther from the foot, the brain activity progressively increased in areas that are linked w/ passive coping w/ distant dangers
        
        • Anterior orbitomedial PFC
    • This reveals the neural circuitry for arachnophobia
  • Davis and Johnsrude 2003
    
    • Used correlation paradigm to further explain the neural underpinnings of intelligible and unintelligible
    • Intelligibility is on a continuum
    • 1. Used fMRI, subjects listened to diff stimuli
         * Undistorted condition
         
         • A: Speech: normal sentences
           * Partially distorted conditions
         • B: Vocoded speech: sentences altered to sound rough but intelligible (similar to Narain et al 2003)
         • C: Segmented speech: sentences altered by dividing the speech stream into separate chunks and replace some parts w/ signal-correlated noise
           
           • These parts retain many original acoustic features but lack recognizable sounds
         • D: Speech in noise: sentences are placed in the background of continuous speech spectrum noise?
           * Completely distorted condition
         • E: Signal-correlated noise: sentences altered in the same way in the “segmented speech” condition
           
           • Here, all of the chunks are replaced w/ signal correlated noise -> so the stimuli is completely incomprehensible
             
             • NOTE: in the 3 partially distorted conditions, there are 3 diff degrees of distortion leading to 3 diff degrees of intelligibility
         • Based on pilot study
         • High intelligibility: 90% of words reported correct
         • Medium intelligibility: 70% of words reported correct
         • Low intelligibility: 20% of words reported correct
    • 2. The subjects pressed buttons to rate the intelligibility of each stimulus on 4-point scale
    • Results of analyses
      
      • Subtraction paradigm: compared distorted condition w/ silence
        
        • Sig bilateral activation in Heschl’s gyrus and surrounding auditory cortices
      • Corelation analyses: see which brain regions respond w/ gradual increase in BOLD signals when the intelligibility of the stimuli increases
      • The following regions show Neural sensitivity to cont variation in intelligibility of stimuli:
        
        • 1. superior and middle temporal gyri in LH; extends anteriorly to temporal area and posteriorly angular gyrus
        • 2. Similar to #1 but distributed more anteriorly in RH
        • 3. Small part of Broca’s area
    • Follow-up analyses
      
      • There is a single voxel in the left anterior temporal lobe that was sensitive to intelligibility
        
        • Activated strongly to undistorted condition
        • Activated weakly in completely distorted condition
        • Activated w/ varying intensities across 3 partially distorted conditions depending on the amount of distortion
          
          • (i.e. 90%, 70%, or 20% intelligible)
      • IOW: the voxel is not sensitive to the diff ways they are distorted (vocoded, segmented, or embedded in background noise)
  • Take away from this study: brain mechanisms for comprehension of intelligible utterances involve the LH areas mentioned in Narain et al 2003’s study
    
    • It also involves the RH
  • Here, the correlation paradigm allows rs to discover more brain areas involved
  • Gradual changes in the stimuli taps into diff brain regions
• Multivariate Pattern Analysis
  
  • A new paradigm that can decode more fine-grained patterns of brain activity to more precision than the other paradigms
  • In the subtraction and correlation paradigms, each voxel is independent, and the analyses shows separate measures of signal strengths
  • When we use these paradigms to look at the whole brain, it looks at the mean response of each isolated voxel in each condition
  • When we use it to look at the region of interest (ROI), it spatially averages the signals from all the voxels in the region for each condition
  • Limitations: this ignores the relationship b/w voxels, and this can’t detect any info that is latent (dormant)
  • MVPA can identify these dormant patterns, and relate them to cog abilities/tasks
  • Mur et al 2009/ Raizada et al 2010
    
    • MVPA can help explore whether the perception of similar syllables (ex. ra and la) is associated w/ distinct levels or patterns of brain activity in the superior temporal ROI spanning 9 voxels
    • If the stimuli triggered orthogonal (right angle) 4-voxel activation patterns in ROI, the conventional analysis would miss this
      
      • Conventional analysis would generate output that shows the same activity for both speech sounds and suggest that ROI cannot discriminate b/w the two
    • MVPA can expose this separate pattern, and suggest the ROI contains at least partially non-overlapping neural voxels that represent the 2 syllables
  • Point: MVPA is very useful
  • Abrams et al 2013
    
    • Used MVPA to examine the neural substrates that process intelligible vs unintelligible utterances w/ better precision
    • 1. Present 20 ppl w/ 2 types of stimuli, sequenced in alternating blocks
         * A: Speech (Sp): Intelligible excerpts from famous speeches in 20 C
         * B: Rotated speech (RSp): same experts but spectrally rotated (inverted) as in Narain’s 2003 study
    • 2. Ppl play close attention to each excerpt and push a button when it ended
    • Rs conducted 2 analyses: Subtraction and MVPA
      
      • I. Subtraction paradigm/General Linear model (A – B) -> (Sp – RSp)
      • II. MVPA, searchlight version
        
        • For every voxel in the brain, a 3 x 3 x 3 neighbourhood is made, centred in the given voxel
        • W/in the 27-voxel space, rs determined is they were diff
    • Results
      
      • Red: conducted subtraction/General linear model (GLM) analysis
        
        • Areas include 3 left lateral temporal regions (as seen in Narain et al 2003)
        • Most of the bilateral temporal regions (as seen in Davis and Johnsrude 2003)
      • Green: MVPA/ searchlight analysis; Also detected by GLM analysis
        
        • There are 2 patches where the multi-voxel patterns of activity were sig diff for the two conditions
      • Blue: MVPA/ searchlight analysis; NOT detected by GLM analysis
        
        • Picked out RH areas the can discriminate b/w the two conditions
        • Located in temporal, parietal, and FL
        • They are associated w/ auditory sensory processing
        • • Conclusion: results suggest MVPA can resolve inconsistencies in the literature by being more sensitive in data analysis

Question 31

Electrophysiology

• 2 Electrophysiological approaches
• 2 ways to record electrical signals of neurons
• # 1 Stimulation
  • Penfield 1956
    
    • How he mapped functional organization of the cortex?
    • Results
      
      • Stimulate Primary somatosensory cortex
      • Stimulate superior temporal regionstimulated higher-order temporal regions
      • Stimulate language related regions 3 effects
        
        • Speech arrest
        • Anomia
        • Paraphasia
  • Ojemann 1989 - directly stimulate language-related areas to map out that cortex area
    
    • Methods - 4 steps
    • 2 main findings
  • 3 cons of e- stimulation
• # 2 Recording
  • Intracranial
    
    • fx
    • procedure - 2 steps
    • Creutzfeldt et al 1989 finding
    • Local field potentials
      
      • What is it
      • 2 ways to measure it
    • Flinker et al 2011 - Studied cortical dynamics of speech perception in 3 epileptic patients
      
      • Methods
      • Results
  • Extracranial
    
    • fx
    • EEG
    • ERP
    • 4 ERP parameters
    • Why is +ve or -ve wave deviations don’t matter?
    • Spatial and temporal resolution
    • N400
      
      • meaning
      • Which electrode can detect N400 w/ greatest amplitude
      • When does it increase
      • Kutas and Hillyard - Showed the waveforms evoked by 3 diff types of sentences presented to subjects on a screen, 1 word at a time
        
        • 3 conditions
        • results

Answer 31

Electrophysiology

• Both PET and fMRI does not directly measure brain activity; they only track the metabolic consequences
• 2 Electrophysiological approaches
  
  • Directly stimulate specific parts in the brain and observe the effects on cognition and b
  • Record electrical signals of neurons
    
    • 1. Intracranially: put electrodes in the brain to record the firing of single cells or a cluster of cells
    • 2. Extracranially: put electrodes n the scalp to record cells firing

Stimulation

• Penfield 1956
  
  • Direct electrical stimulation to map the functional organization of the cortex
  • Did this on patients’ w/ epilepsy before removing the brain areas that were thought to cause seizures
  • Used local anaesthesia only as there are no pain receptors in the brain
  • Found that stimulating some areas induce “+ve responses”
    
    • Ex. stimulate PMC cause involuntary movements in specific body parts
    • Ex. Stimulate Primary somatosensory cortex evoked feelings in specific body parts; they correspond to the somatosensory homunculi
    • Ex. Stimulate occipital regions cause visual hallucination (color, starts, light flickers)
    • Ex. Stimulate superior temporal regions cause auditory hallucinations (ringing, clicking, buzzing)
    • Ex. If he stimulated higher-order temporal regions, this replays the patient’s past experiences that were richer than ordinary recollections
      
      • flashbacks/dreams
      • This is rare
  • Stimulation to language-related areas can induce “-ve responses”, esp for speech
    
    • Speech arrest: slowing of speech production
    • Anomia: can’t retrieve a word
    • Paraphasia: distort the semantic or phonological content of a word
      
      • Ex. say “tephelone” instead of “telephone.”
  • This showed that stimulating specific sites and cause linguistic errors
• Ojemann 1989
  
  • directly stimulate language-related areas to study language
  • mapped out the “eloquent” cortex in the left perisylvian territory
  • 120 patients w/ epilepsy
  • 1. Showed line drawings of familiar objects on a screen in 4-sec intervals
  • 2. Patient had to name each one using the carrier phrase “this is a ___”
  • 3. At the beginning of some slides, the rs stimulate one of the several predetermined points on the exposed cortex
       * Each part was stimulated 3 times; w/ all sites were stimulated once b4 any of them were stimulated a 2^nd time
  • 4. Rs provide immediate feedback on patient’s response
       * If stimulating a given site induced error for 2 out 3 trials, that site is essential for naming
  • 2 main findings
    
    • 1. For most cases, stimulation disrupted naming as a few discrete sites
         * In 70% patients, 2+ of these areas were identified: 1 in FC, other in temporal/parietal cortex
    • 2. Rs did stimulation mapping on 90 patients in anterior and posterior perisylvian zones
         * 20% had frontal naming sites
         * 15% had temporal and parietal naming sites
         * Main point: precise naming sites in the brain vary across patients
         * There was only 1 site where errors were evoked more than 50% of the time (located in posterior part of Broca’s area)
• Some say electrical stimulation is the “gold standard for brain mapping”
• Cons:
  
  • 1. we don’t fully understand the physiological cons of passing current through the cortex
  • 2. The intensity of stimulation that is needed to identify “eloquent” areas differ across patients and regions
  • 3. Stimulation to a given site can propagate to other remote brain regions
• Need to interpret these findings w/ caution!

Recording

• Intracranial
  
  • Some rs record neural activity in particular regions
  • It helps doctors to precisely localize the source of epileptic seizures
  • Procedure
  • 1. Implant electrodes in the tissue that is suspected to surround the epileptogenic site
  • 2. close the patient’s head and record neural activity for several days cont
       * If the seizure occur, we can identify the point of origin
  • Some rs determine whether and how the firing rates of neurons in the implanted tissue are modulated (regulated)
    
    • They study the neural activity in single cells of cell assemblies
  • Creutzfeldt et al 1989
    
    • Found that individual neurons in the right superior temporal gyrus are sensitive to certain features of auditorily perceived words (ex. phoneme, syllables, morphemes)
    • Ex. when the patient listened to a list of multisyllabic words, the firing rate of one cell increased sig in response
    • The critical sounds are velar consonants (i.e. /k/, /g/) combined w/ /r/ or /s/
      
      • Ex. Christmas, crocodile
    • When the entire list of words was presented again after 2 min, the cell’s response to each word was similar to the response in the 1^st time
  • Local field potentials: the sum of the extracellular voltage fluctuations that indicate the sum of events in the dendrites for a local population of neurons
    
    • This is measured when the patient is doing linguistic tasks
    • Methods
    • Option A: Use electrodes that penetrate many layers of cortex and white matter/ or target subcortical nuclei
    • Option B: use high-density multi-electrode grid, place it directly over the cortical surface to collect data (aka electrocorticography)
  • Flinker et al 2011
    
    • Studied cortical dynamics of speech perception in 3 epileptic patients
    • 1. Placed an electrode grid on patient that covers the posterior lateral surface of the left superior temporal gyrus
    • 2. Ppl listened to 2 types of stimuli
         * I. Syllables (for 150 ms): /ba/, /da/, /ga/
         * II. 3 kinds of words spoken by the same talker
         
         • 23 pseudowords (3 phonemes)
         • 23 real words (3 phonemes)
         • 4 proper names (5 phonemes)
    • Results:
      
      • Electrode A (top row): high frequency neural activity response only to words
      • Electrode B (bottom row; 4mm away to electrode A): high frequency neural activity response to both words and phonemes
      • Most activity starts after 200 ms
    • Point: electrocorticography is useful
• Extracranial
  
  • Electrical potential produced by large populations of neurons are strong enough to be conducted passively though tissues of the brain, skull, and scalp
  • This is a method to record patterns of activity in a non-invasive manner
  • You place electrodes on the surface of the scalp and compare the voltage fluctuations here w/ a reference location (ex. mastoid bones behind the ears)
  • Electroencephalogram: recording on the changing electrical activity; data is from an electrode on the scalp
    
    • Has rhythmic undulations (ups and downs) that vary in amplitude, duration; it depends on whether the subject is excited, relaxed drowsy or in a stage of sleep
  • EEG is a collection of many diff neural activity; so it doesn’t provide info on mental operations
    
    • Rs examine the neural correlates of specific cog capacities
    • Rs examine how the EEG recorded at diff electrodes change when ppl are doing the tasks
  • Event-related potentials (ERPs): EEG patterns that are measured when the stimuli is presented
  • 4 ERP parameters
    
    • 1. Latency: time-point, milliseconds after the stimulus; happens when a particular deflection of waveform begins/reach its peak
    • 2. Amplitude: strength of an effect (mV)
    • 3. Polarity: whether a deflection is +ve-going or -ve-going
    • 4. Topography: the scalp distribution of an effect; involved the electrode positions at where the effect was observed
  • Some labs plot -ve up and +ve down OR vv
  • When a wave deviates +vely or -vely, it usually is not sig
    
    • This is b/c polarity is affected by many irrelevant factors
      
      • Ex. location of reference electrodes
      • Ex. orientation of the source of scalp recorded signals
      • Ex. if a batch of cortical neurons have their dendrites point to the surface and simultaneously get excitatory input, the resulting electrophysiological activity create current “dipoles”
        
        • Each dipole has a -ve end near the dendrites and a +ve end near the cell body
      • The summation of these dipoles is detected at the scalp as a -ve voltage
      • This does not mean the operations are done by the neurons, it’s just activity on detected on the scalp
    • Since most ERP studies compare waveforms from the experimental to control condition, the diff in polarity maybe related to cog processes
    • The key thing is there is a polarity diff; the +ve/-ve doesn’t matter
  • Topography
    
    • Studies vary on the # of electrodes used and their size
    • As the size increases, the difference of ERP effects along the scalp increases
    • The larger range of channels, the easier it is to apply data analysis to somewhat infer the neural underpinnings of ERP effects
    • Inverse problem: ERP has poor spatial resolution but v good temporal resolution
    • Another issue: the electrical activity recorded at the scalp can come from any neural generator
  • N400
    
    • N = negative
    • 400 = a peak that appears 400 ms post-stimulus
    • centroparietal electrode can detect a N400 w/ the greatest amplitude
    • N400 can track the gradual build-up of semantic content during receptive sentence processing
      
      • The amplitude increases as we increase the difficulty of integrating the meaning of a word into the preceding context
    • Kutas and Hillyard 1980
      
      • Showed the waveforms evoked by 3 diff types of sentences presented to subjects on a screen, 1 word at a time
      • Condition 1: all sentences are normal
        
        • Ex. It was his first day at work
      • Condition 2: all of the sentences ended w/ a word that was semantically anomalous in the given context
        
        • Ex He spread the warn bread w/ socks
      • Condition 3: all the sentences ended w/ a word that was orthographically incongruent in the given context
        
        • Ex. She put on her high heeled SHOES
      • Results: final word in anomalous condition trigger a large N400
        
        • This indicates there was effortful conceptual processing, not surprise
      • The final word in the orthogonal condition is associated w/ a P560
        *

Question 32

Magnetoencephalography

• Which technique is it related
• Mechanism
• ERFs
• What sensors are used?
• What does SQUIDS stand
• 2 Pros of MEG/ERF
• 2 Cons of MEG/ERF
  *

Answer 32

Box 2.2: Magnetoencephalography

• Non-invasive brain mapping technique related to EEG/ERP
• Electrical currents associated w/ neural activity create tiny magnetic fields, these fields are recorded at the scalp and time-locked to when the stimuli is presented
• This produces event-related fields (ERFs)
• In MEG systems, we detect ERFs w/ 200 sensors called SQUIDS
  
  • SQUIDS: superconducting quantum interference device
• Pros of MEG/ERF
  
  • Outstanding temporal resolution (in ms)
  • Provide good spatial resolution, can help neurosurgeons identify where the seizure happens in epileptic patients
    
    • This is possible b/c magnetic fields are not distorted as they pass through the brain, skull, and scalp
    • Magnetic field strength dips from their source in a systematic manner
• Cons
  
  • It is sensitive to neural activity in the gyri but NOT the sulci
  • Too $$$
    
    • This is b/c ERFs are tiny signals that are a billionth the size of earth’s magnetic field
    • The lab has to be heavily shielded from outside magnetic fields
    • SQUIDS need to be stored in liquid helium
• More studies are using this despite the cost

Question 33

Transcranial Magnetic Stimulation

• 2 reasons why it is not often used
• What can it do
• Is it safe?
• Mechanism
• Temporal and spatial resolution
• What doe researchers use as a benchmark
• 2 strategies are used to determine the appropriate position of a coil (can use 1 or both)
• Major unkown issue
• Define online vs offline application of TMS
• Gough et al - Used TMS and found the complementary roles of 2 diff sectors in the left interior frontal gyrus (LIFG) in making semantic and phonological judgements
  
  • Methods
  • Results
    *

Answer 33

Transcranial Magnetic Stimulation

• It is very invasive and restricted to those w/ a history of nro dysfunction -> TMS is not used often
• TMS can quickly alter the organization of neural activity in certain cortical regions by placing magnetic device on the scalp
• You can facilitate or supress the operation of the target area
• If safety protocols are followed, TMS is harmless; w/ may cause seizures
• It can help offset clinical disorders like stroke-induced aphasia, and study language/MD

How It Works

• Uses EM iniduction
• Faraday
  
  • When an electrical current passed thru a wire, it generates a magnetic field that varies w/ time
  • If wire 2 is placed nearby, the magnetic field induces an electric current flow in wire 2
• For TMS, “wire 1” is the stimulating coil”; “wire 2: is the targeted region of the brain
• Common coil type: figure-8 shape, current flows around 2 adj parts and sum up at the intersection
• The flux/magnetic field lines are perpendicular to the plane of the coil
• • When the central part of the coil is placed at a predetermined position on the scalp, the magnetic field that passes through the skull
    
    • this temp changes the electrophysiological properties of the neurons under the cortical region
• • Temporal resolution: ms
• Spatial resolution: mm
• Shifting the coil b/w areas separated by .5 to 1 cm over the PMC can trigger muscle twitches that follow the motor homunculus layout
• Rs use the intensity threshold for triggering a finger twitch as a benchmark for calibrating the strength of pulses delivered to other regions for high-lv cog processes
• 2 strategies are used to determine the appropriate position of a coil (can use 1 or both)
  
  • 1. Functional localization: move the coil around a general territory until the ability of interest if enhanced/disrupted
  • 2. Anatomical localization: use neuronavigation system to guide the placement of the coil
       * based on data from structural or fMRI OR a set of standardized coordinates
• Issues: effects of TMS can spread to remote brain regions; there may be other b cons
• • There are many factors that induce facilitatory or inhibitory effects
• One main parameter: frequency of pulses
• Ex. 2 single pulses separated by less than 5 ms -> intracortical inhibition
• Ex. 2 single pulses separated by 10 – 30 ms -> intracortical facilitation
• Some pulses can be applied to subjects “online” (during the task performance)
• Some pulses are applied “offline” (prior to task performance)
• Ex. Common technique – apply repetitive pulses to target site cont for several min b4 task
  
  • Reduce excitability of that region after stimulation
  • This can affect subsequent performance
• TMS cons are measured in RT or accuracy

Applications to Language

• TMS helps us understand more about language-related brain regions
• Gough et al 2005
  
  • Used TMS and found the complementary roles of 2 diff sectors in the left interior frontal gyrus (LIFG) in making semantic and phonological judgements
    
    • Rostral (pars orbitalis)
    • Caudal (pars opercularis)
  • Subjects did 3 task w/ visually presented pairs of letter strings
    
    • Synonym judgement – ex. decide if idea and notion hv the same meaning
    • Rhyme judgement – ex. decide if eye and fly end w/ the same sound
    • Visual judgement – ex. decide if txbufr and txbufr have the same characters
  • There are 15 pseudo-randomly organized blocks of 10 trials, w/ the trials in each block involving the same type of task
  • 40% of the trials
    
    • There are 3 TMS pulses separated by 100 ms and starting 100 ms post-stimulus onset
    • These were delivered to the rostral or caudal of LIFG
  • There are equal # of TMS trials for each task; no more than 2 TMS trials consecutively
  • Results
    
    • Double dissociation emerged b/w semantic and phonological tasks based on the function of the site of stimulation
    • Judgements on the meanings of word pairs are delayed by rostral LIFG stimulation, not caudal LIFG
    • Judgements on the sound of word pairs were sig delayed by caudal LIFG stimulation, not rostral stimulation
    • Judgements on the appearance of letter strings were not affected by either site
  • There are 2 target areas in the LIFG that make diff contributions to lexical processing
  • These areas are close together; TMS can modify brain activity of brain areas that are close together
    *

Question 34

Major Strengths and Weaknesses of the Different Methods

• Method
• Strength
• Weakness

Answer 34

Question 35

What is language

• Compare and contrast
  
  • Zebra Finches vs humans
  • Monkey Alarm clocks and Zebra Finches
    *

Answer 35

What is language

• Examples of communication (i.e., there needs to be some interaction between multiple individuals, usually of the same species, to communicate info):
• Ex. Zebra Finches: male communicating (mate calling) with a female
  
  • The sounds are sequences of predictable sounds (aka motives)
  • There is enough similarity b/w Zebra finches and humans when communicating
  • It lacks some aspects of communication (ex. we don’t know what is being said)
• Monkey Alarm Calls: aka notifying each other of a predator
  
  • Monkeys have different alarm calls for different predators
    
    • Alarm call 1: leopard alarm call
    • Monkeys from different species recognize each other’s alarm calls
    • They will move closer b/c once the leopard knows it has been spotted, it will give up
    • Unlike the zebra finch, we know what is being said (leopard is here)
    • Communication here is more sophisticated
• These are not perfect examples of language
• Main point: there is a continuum of communication; the more complex form is used in humans

Question 36

Neural basis of language

• What is the brain’s language network made of?
• What are these other systems also used for?
• How do we understand words: 5-step

Answer 36

Neural basis of language

• The brain’s language network is formed by a combination of areas (networks) of brain regions that have become differentially specialized for language, but that clearly also relate to other basic cognitive abilities
• Different systems are used in different aspects of language; these brain areas are also used in other functions (non-language)
  
  • Vision (ex. reading)
  • Audition (ex. listening)
  • cross-modal associations
  • motor outputs (ex. writing, Brail)
  • planning/executive control (ex. produce a response)
• How do we understand words?
• 1. Extract words from auditory segment
• 2. Separate them into phonemes
• 3. Associate these to words
• 4. Put words together to determine its meaning
• 5. Produce a response
• If certain language functions are present in other species (like birds and monkeys), these functions may evolved to be more specialized in humans

Question 37

A few (of many!) properties of language

• 6 main properties

Answer 37

A few (of many!) properties of language

• “words” convey “meaning” (lexical semantics)
  
  • Ex. monkeys has a specific alarm for leopards (basic meaning)
• Grammar, morphology, and syntax (particular words in particular order)
  
  • Ex. not present in monkey language (subject, verb, object structure; location of leopard)
• Generative (i.e., we can create new sentences that everyone can understand)
  
  • Ex. not seen in monkey speech
• Specialized for communication
  
  • Ex. human language is used for communication specifically
  • Ex. Hammer is not specialized for communication – can be used as an alarm, or banging on a pot for music
• BUT, it stills builds upon other basic abilities like vision, audition, and motor systems, to name a few
• Other important properties?

Question 38

Cognitive Neuroscience of Language

• 3 major domains for this discipline
• What are the 4 other areas
• How of other areas contribute to this realm?
  
  • Evolution / Cross-species comparisons
  • Historical analyses (e.g., of language evolution)
    
    • Study: Compare Spanish in Europe vs South America
      
      • Looked at hominins (ambiguous words)
      • Define hominins
      • Method
      • Results
  • Computational Modeling
    
    • Neural network simulation
    • 3 Pros
  • Genetics

Answer 38

Cognitive Neuroscience of Language

• Fundamentally, an interdisciplinary domain, comprised of at least 3 major domains:
  
  • Cognitive psychology
  • Neuroscience (Neuropsychology = precursor to NRO)
    
    • Neuropsychology: post-mortem study on what aspects of the patient is impairing language
  • Linguistics
• Although many other areas make their appearance as well:
  
  • Evolution / Cross-species comparisons
    
    • Behavioral, neural levels
    • Some rodents can detect similar sound frequencies as humans
  • Historical analyses (e.g., of language evolution)
    
    • Tells us…
      
      • how words change meanings over time
      • how new words are come about
      • Why different communicative abilities evolve
      • what words are central to communication; what words are less relevant
    • Study: Compare Spanish in Europe vs South America
      
      • Looked at hominins (ambiguous words) – these words have different meaning based on the context they are in
      • Ex. river BANK vs money BANK
      • Results:
        
        • 50% variability in the language remains the same in two populations
        • 50% variability in the language - the meaning has changed
        • Reason: distinct cultural env, ext env, colonization in South America changed some meanings of words
  • Computational Modeling
    
    • Neural network simulation: dev an algorithmic or math model of how language works in the brain
    • Pros
      
      • Develop complex theory
      • Allows us to make predictions for empirical studies
        
        • Helps us to know what to study next
      • Allow us to do things that may be unethical on real subjects
        
        • Ex. damage a brain part in the model, and see how the model reacts to the damage
        • Ex. examine if therapy works for brain damage
          
          • Give different types of therapy to brain damaged model and see how it reacts to each one of it
          • Then test and apply this to humans, and see if it works
  • Genetics
    
    • Looks at how single and combination of genes leads to different amounts of NT, which in turn may impact our language processing
    • Ex. Diff types of dyslexia may linked to different collection genes; this can be related to whether the guy or gal contributed the genes

Question 39

Classic examples

• Broca vs Wernicke aphasia
• Corresponding BA #s?
• Which hemisphere is more specialized for language?
  
  • which type of language?
• Audiovisual integration
  
  • low lv vs high lv?
• Amodal semantic combination
• Articulatory planning
• Volition
  *

Answer 39

Classic examples[EL1]

• Broca’s and Wernike’s Aphasias
• In many ways, the seeds of the current interdisciplinary science of language research
• Behavioural Manifestation:
  
  • Broca: meaning intact, but not the sentence structure
    
    • BA. 44 and 45
  • Wernicke: no meaning, fluid speech (word salad)
    
    • BA 42
• Very different language impairments, linked to different brain impairments

A basic map of some language systems

• Note: Many areas serve more than one language relevant or non-relevant ability
• Most of our cortex influences our language
• LH is more specialized language, esp visual language
  
  • Visual inputs, auditory inputs, audiovisual integration
  • Audiovisual integration
    
    • Low level: how movement of lips correspond to different sounds
    • Higher level: read text on the screen (subtitles) interact with the dialogue the actors is speaking in the movie
  • Amodal semantic combination: how we map info from one modal to another
    
    • I pat a dog, it feels furry; and you can hear the word “fur”
  • Articulatory planning: plans how to move our mouth to produce specific sounds
  • Volition: decide what we want to produce
•  Language processing and production is a very complex task, yet our brain has come to do things very efficiently and effectively

[EL1]Understand the difference between the two aphasias

Know where the brain regions are located

Question 40

Tools of the trade

• Neuropsychology
  
  • 3 main ways
• Psycholinguistics/behavior studies
  
  • McGurk effect
    
    • Which 2 systems are used?
    • What does this indicate?

Answer 40

Tools of the trade

• Language processing is extremely rapid (ex. when you hear multiple words per second) and takes place across a distributed set of brain regions
• These brain regions also subserve other abilities (e.g., auditory system is not only for language)
• What types of methods can be used to probe language?

Neuropsychology

• We study patients with language impairments, link those to brain damage, usually originally primarily through post-mortem analyses
• but sometimes we study living individuals like Phineas Gage).
• Now, the brain is also explored through non-invasive techniques except in special circumstances (e.g., implant electrodes in pre-surgical epileptic patients’ brain).

Behavioural Studies (aka Psycholinguistics)[EL1]

• E.g., the McGurk effect
  
  • We use different information from the visual and auditory modality to perceive an ambiguous stimulus
• Can provide important insights and constraints on cognitive and neural theories of processing
• These types of tasks are often used in conjunction with other cognitive neuroscience techniques (e.g., ERP).

• [EL1]Understand how there are different systems contributing to language at the same time, some may be more powerful or relied upon more
• McGurk effect is a great example of this

Question 41

Tools of the trade cont 2

• ERP
• Pro, con
• Steinhauer, 2014, Applied Linguistics
  
  • Method
  • Results

Answer 41

ERP

• Behavioural studies are precursors of imaging studies
• Pros: Excellent for studying fast processing, which is common in language (we need good temporal resolution; helps us track changes over time).
• Cons: Relatively poor spatial resolution (without convergent evidence from other techniques/studies, data alone only tell you roughly which quadrant of the brain the signal came from).
  
  • Don’t know the precise location where the signal is coming from

Example from Steinhauer, 2014, Applied Linguistics

• Method:
  
  • 1. Put on EEG cap
  • 2. Listen to sentences
       * Ex. John ate broccoli at dinner
       * Ex. John ate democracy at dinner
• Results
  
  • Blue vertical line: onset/when the words (i.e. broccoli or democracy) are spoken
  • Results: brain signals look similar overall, except at N400 (blue = difference)
  • N400: (400ms after onset)
    
    • There’s a difference b/w processing the word that makes sense vs one that doesn’t make sense
    • N400 relates to how comprehensible the sentence is

Question 42

Example of Combining Behavioural and Neuroimaging Techniques

• Baart, Armstrong, Martin, Carreiras, and Frost (2017)
• Exp 1
  
  • Methods
• Exp 2
  
  • Methods
  • How is it different from Exp 1
  • Purpose
• 4 noise conditions
• Results of behavioral exp 1
  
  • Accuracy & RT
  • Is having a lot noise as bad as predicted, why?
• Results = ERP Exp 2
  
  • Analysis
  • What it suggests
• 4 main insights

Answer 42

Example of Combining Behavioural and Neuroimaging Techniques

• From Baart, Armstrong, Martin, Carreiras, and Frost (2017)
• • Method[EL1]
    
    • Exp 1: behavioural experiment
      
      • 1. See and hear a Spanish word (ex. Apio)
      • 2. Press a button if what they see and hear match
      • Participants had to go through 4 conditions
        
        • no noise
        • audio noise
        • visual noise
        • audio and visual noise
    • Exp 2: same experiment but measure subject brain activity w/ EEG
      
      • Only difference: there is a 1250 ms b/w read + listen to word and pressing the button
      • Purpose: the actual act of pressing the button will activate the motor cortex
      • this delay allows researchers to differentiate b/w when the brain is reading + listening to the word vs pressing the button
• Noise conditions
  
  • No noise: white text on black background
  • Visual noise: white dots on the “white text and black background”
    
    • • Audio noise
    • Ex. play a random audio noise -> most ppl don’t know what word it is saying
    • When someone told me the word is “actress”
      
      • It seems obvious the word is actress in retrospect
    • This suggests that when the audio information is not clear, presenting the word visually can clear up the ambiguity
  • A + V noise (have audio and the visual noise presented)
• Results – behavioral exp 1
  
  • • Accuracy & RT: Ppl are the most accurate and fastest when there is no noise
  • Auditory noise makes ppl slightly less accurate and a bit slower
  • If you have more noise (i.e. A + V noise), you are the least accurate and the slowest
    
    • But the effect is not as bad as it seems
      
      • When we look at RT, AV noise is significantly slower compared to no noise
      • For accuracy, the drop is not as bad
• Results = ERP Exp 2
  
  • Researchers did a lot of t-tests
  • After controlling for this (the orange and blue), we get the results (black)
  • The effects happen around N400 (~500 ms)
  • This suggests that the integration of audio and visual noise is happening at the understanding/later semantic level (not early perceptual level)

Integrating insights

• Combined data point to cross-modal integration occurring at a relatively late time-point, at the level of lexical/semantic processing
  
  • (combining info from 2 modalities happen later)
• Surprisingly, the constraints from sublexical units (individual letters / sounds) seems relatively weak. (most integration happens at lexical semantic lv)
• Potentially due to language tested (Spanish).
  
  • Transparent orthography: every letter maps onto a particular sound, and vv
  • Results may not apply to other languages that do not have transparent orthography (ex. Eng, Hebrew)
• Points to value of Cross-linguistic comparisons another type of study that transcends any particular technique
• • *

[EL1] Understand these experiments well and the significance of their results