Cognitive Neuro Exam 1

starting point

mind is immaterial and can’t be measured, only through introspection

behaviorism

• pretends mind doesn’t exist.

• Strictly stimulus -> response 

cognitive psych

• stimulus -> cognition -> response 

• Allow us to engage in problem-solving 

• Can’t study any of the principles on their own, have to think about how they all play together

  • memory, attention, emotion, language, perception 

neuroscience

• study of nervous system

• no regard to mind

• Biological mechanisms 

cognitive neuroscience

• study of how the brain enables the mind 

• Brain lesions, brain stimulation, neuroimaging to understand how diff aspects of cognition relate to brain function 

• No 1 to 1 mapping between cognition and anatomy 

lesion studies

• Observing deficits in pts that have damage to certain areas. 

• fundamental to core theories in cog neuro

  • phineas gage, Tan (broca’s aphasia), HM (bilateral hippocampus removal)

• focal damage more revealing than diffuse

• evidence from diff studies accumulate across methods 

broca’s aphasia

• affects how you speak but language comprehension is intact

• understand what is being asked

• focal lesion in left inferior pfc

• doesn’t support aggregate field theory

  • showing what one area can do, another can’t

balint syndrome

• problem w/ attentional systems

• can only see one thing in visual field. 

optic ataxia

• can’t use visual cues to make movements

• doesn’t know where things are in space

clive wearing

• no short-term memory.

  • Can’t think of past or future w/ himself in it. 

• No hippocampus 

• No episodic memory 

• Has procedural mem and semantic knowledge 

brain stimulation

• Ex: electrical stim in patient that can’t recognize faces. 

• Ex: stimulating during brain surgery to make sure speech is intact 

modular

• given brain region enables specific cognitive function 

• Ex: hippocampus supports episodic memory 

distributed

• cognitive processes reflect interactions among multiple brain regions 

• Regions act in concert for diff cognitive services 

• Supported by default mode network 

phrenology

• brain organized around diff functions that are distinct from one another.

  • More well developed the function, the more well develop organ that enables it (reflected in contours on the skull) Part will be larger if you are better at it 

  • Supports modular brain 

  • By Franz Gall (1810) and planted seed of modular mind embedded in modular brain  

Marie-Jean-Pierre Flourens

• napoleon commissioned x to disprove Gall’s modular brain

• lesioned brains of pigeons and rabbits

• focal lesions had no apparent impact on animal

• aggregate field theory

aggregate field theory

• faculties of the mind are distributed throughout the brain

• suggests whole brain supports cognition (distributed)

• marie-jean-pierre flourens lesioned brains of pigeons and rabbits

wernicke’s aphasia

• can’t comprehend language

  • right cadence, rhythm, gestures but what they say doesn’t make sense

    • words they use don’t have intended meaning

• focal lesion in left superior temporal lobe

• size of lesion doesn’t necessarily predict severity

karl lashley

• sought to find engrams in brain

• trained rats to run a maze then removed part of their brain

  • varied sizes of lesions

• maze performance was unaffected by location of lesion, instead size mattered

• supports distributed brain with law of mass action

engram

• physical change in brain that corresponds to learning episode

• still don’t know if it is real

law of mass action

• aka equipotentiality

• all brain regions contribute equally to all cognitive functions

• rephrased aggregate theory

• result of Lashley lesioning rats after learning maze

penfield

• 1950s neurosurgeon for epilepsy

• montreal procedure to treat

  • mapping brain by stimulating (electrode) and asking pt to describe what happens

  • excise epileptogenic brain areas

    • cures seizure in most cases

  • aura is clue to area seizure is originating from

• supports modular brain; all pts experiencing same sxs in same regions

H.M.

• Brenda Miller determined seizures were caused bilaterally

• removed hippocampus bilaterally

• mostly cured of seizures but very amniesic

• episodic mem impairment

• found diff brain regions support diff kinds of mem

  • procedural mem intact

  • made fewer errors on task despite not remembering ever doing it

mosso

• observed pulsations of veins on surface of brain changed depending on what pt was doing

• how blood flow in brain is related to cognition

• inferred blood flow inc w mental activity

• studied ppl w congenital malformations—pieces of skull missing

• beginning of neuroimaging

human brain circulation balance

• origin of neuroimaging

• created by mosso to measure hemodynamics in brain

• head tipped down when pts began performing math in mind

• no relation to specific brain region

fulton

• went beyond Mosso and said localized inc in blood flow to brain areas in high demand

• pt Walter K had congenital vascular malformation in close proximity to visual cortex

  • could hear flow of blood when eyes were open but not when they were closed

fMRI

• measures distribution of oxygenated blood in brain when completing cognitive tests

  • doesn’t measure neural activity

  • reveals brain function

• supported notion of functional specialization

• supports modular and distributed

• strictly correlational no causal claims

• high spatial rez, low temporal

  • shadow that doesn’t emerge til ~10 seconds after cognitive task is complete

network-based fMRI

• shifted towards distributed perspective

• default mode network

  • activity in these regions connected—1 goes up, activity goes up in other

  • goes up w/ fixation cross/letting mind wander

  • goes offline when shown stimulus outside of brain

single-cell recording

• put electrode into neuron

• invasive

• very limited experimental freedom

  • clinical populations only (typically epilepsy pts)

• high temporal and spatial rez

• measures APs

• limited to max of 10 neurons

  • don’t get picture of whole brain

• direct measure of brain activity

• doesn’t require lot of computing and storage

BOLD

• Blood oxygenation level dependency

• modulation of signal intensity over time depending on lvl of deoxygenated blood

EEG

• measures local field potentials NOT APs

  • bc so many fire together they add up

  • electrical changes outside neuron in extracellular space

• unmyelinated dendrites are leaky and allow for detectable voltage changes outside

• great for research trying to find when smth takes place

  • great temporal rez

• not computationally demanding

• inexpensive

• direct measure of brain activity

• look at whole brain

MRI

• reveals brain anatomy

• high rez

• clinical to see damage in region and size of structures

mri magnet

• static magnetic field generated by an electromagnetic coil

• always on

• large electromagnetic coil

• precursor of imaging

• align protons in low energy state defined by high electromag field

resonance

• energy pulse applied at resonant frequency of targeted atomic nuclei (H protons) by a radiofrequency coil

• based on known properties of H

• RF coil alternates btwn stimulating and recording brain

  • not built into machine for research

• reflects relative amts of protons in diff tissues

  • more hydrogen = stronger signal/brighter image

    • collectively emitting rf energy

imaging

• modulate the static magnetic field w a second set of electromagnetic coils (gradient coils)

• allows us to localize signals and generate an image

bore

• where subject lies in mri machine

• where current runs through coil and generates a magnetic field

H protons

• spin and produce tiny magnetic fields

• randomly oriented under normal conditions

• static mag field brings atomic nuclei into spatial and temporal alignment

  • all oriented parallel to long axis of bore of scanner

rf excitation

• targeting protons in low energy state and stimulating them in specific ways

• protons pushed to high energy state 90 degrees

rf reception

• rf emitted is same freq as pulse delivered

• protons return to low energy state

• measure rf emission coming out of brain at same freq as pulse delivered

gradient coils

• introduce heterogeneity in static mag field in terms of magnetic field strength

• define 3-D space in terms of voxels

  • diff signal assigned to each

• localize RF emissions to diff cubes in scanner

• creates predictable differences in RF emissions

at rest

• oxygenated blood is converted to deoxygenated blood at a baseline rate

• use oxy to extract energy from glucose

active

• circulatory system overcompensates for demand

• resulting in proportionally more oxygenated blood than at rest

• vasculature is dilated to great degree and shifts balance of deoxy:oxy

astrocytes

• dilate or constrict local vasculature

• in response to signals from neurons

hemoglobin

• has magnetic properties that differ depending on whether it is bound to oxygen

  • neutral when carrying oxy

  • small mag field of its own when giving away oxy

    • distorts alignment of hydrogen ptns w static magnetic field

    • impacts signal intensity

oxygenated blood

• causes protons to return to their aligned state more quickly and remain synchronous for longer (stronger signal)

• local presence of x = stronger MRI signal

deoxygenated blood

• causes distortion of alignment of hydrogen protons with static magnetic field

• distortion alters effect RF pulse has on nearby protons

  • less synchronous spin and slower return to low energy state

    • weaker signal

fmri resolution

• spatial resolution:

  • very good

  • defined by size of voxels

    • if voxels smaller, more measurements in same space

• temporal resolution

  • terrible

  • not measuring neural activity

  • been seconds since cognitive action was complete

blocked design

• all trials of given condition are clustered

• time varies depending on demand

• rapid succession show images and measure bold response on each stimulus

  • slowly changes over time

BOLD in blocked design

• way to detect differences btwn conditions

• can’t make inferences/differentiate trials w/in condition

• sustained peak = stable, reliable response

  • sustained prolonged estimate of brain activity in each voxel, no fluctuations

event-related design

• baseline varies, duration btwn trials changes as trial goes on

• allows us to recover BOLD that corresponds to individual trials

• pseudorandomly distributing across scan

  • order of conditions mixed together

• requires lots of trials/repetition, longer experiment

BOLD in event-related

• way to detect differences between exemplars not between conditions

• individual responses to individual trials

• BOLD is free to go up and down,

  • can say peak corresponds to x stimulus

subtraction logic

• design doesn’t matter

• detect stimulus | discriminate species | press button

  • SUBTRACT |detect stimulus| and |press button|

  • left with discriminate species

• ex: subtracting average across baseline from avg across test condition

baseline is critical

• can’t make causal claims if it isn’t good

• don’t know if brain region responds to other categories that were not presented

• can see more constrained area w better x

fMRI limitation

• a lot of noise, some areas more difficult to image than others due to proximity to air cavities

• a lot of observations per participant

  • ~576 milllion

  • get a lot of false positives

  • noise in the right voxels by chance

• doing exact same thing can produce diff patterns in the brain

  • have to generalize across people and across time in same person

forward inference

• manipulate what happens in scanner (conditions) and get result

  • where BOLD response is greater for what you are testing than baseline

• good

reverse inference

• have result and infer cause from it

  • not manipulating anything, result informed by pre-existing knowledge

• not supported on empirical basis

• ex: ambigious image where you don’t manipulate what they see. you get result and assume they were seeing x when you don’t know what they were perceiving/doing

fmri cons

• low temporal rez

• correlational evidence - indirect measure of brain activity

• takes a lot of storage and computing

• very expensive

• one data set can produce ~34000 different results

  • can spend so long analyzing 1 data set

hippocampal place cells

• fire really selectively and when rat is in specific location

• x implicated in way-finding

• single cell recording of 10 place cells

  • can build map in brain as to what rat’s x looks like

  • can disrupt reactivation during sleep w/ electricity and rat won’t remember

grandmother cell

• single neuron where ability to discriminate btwn 2 ppl resides

• extreme orthogonal organization (doesn’t interfere w anything else)

• only fires when shown specific person (Halle Berry cell)

  • fires when shown caricature and in costume

• inefficient way of coding

  • if cell dies, can’t remember x person

  • suggests finite amt of knowledge

• single cell recording experiment

importance of pyramidal orientation in eeg

• orderly config allows individual currents to add up together instead of cancel out

• parallel to each other

• perpendicular to scalp

eeg recording

• charge difference during post synaptic potentials creates dipole

  • for epsp, inside gets positive and extracellular negative

  • for ipsp, inside gets negative and extracellular positive

• clusters of pyramidal neurons have charge that adds up and creates dipole with other cluster

  • 2 electrodes detect difference in charge btwn 2 areas

  • detected bc E field propagated through neural tissue

• not just 1 dipole, and not oriented to one another

  • cancel and add

  • change location and orientation rlly fast

• ~1 measurement per millisec of voltage distribution across scalp

• brain, dura, skull, and skin passively conduct electrical currents generated at synapses

• high sampling frequency

eeg data

• looking for changes in voltage over time

• high sampling frequency

• signal embedded in wave forms

  • oscillate from positive-going to negative-going

event-related potentials

• avg voltage for each electrode across MANY repetitions from at least 2 conditions

• signal vs noise

  • noise cancels itself out across trials

• averaged waveforms that are regular in terms of time and direction

  • (+) and (-) don’t mean much on their own

  • get smooth waves linked to stimulus

• waveform centered around 1 electrode (measured voltage change is strongest at specific and drops off at neighboring)

• Think of as '‘event-related voltage changes over time”

ERP naming

• (+) going = P

• (-) going = N

• # corresponds to time peak occurs after stimulus onset

  • in millisec

eeg forward problem

• predicting what electrical voltage will look like on scalp based on known, hypothesized source inside brain

causal methods

• showing brain region supports cognitive function

• through lesion studies

premorbid functioning

• methodological consideration

• lack of knowledge of how pt was before brain injury

• in cog neuro, make assumption that they didn’t have cog deficits prior to injury

• reliance on clinical interviews, autobiographical facts, and second-hand reports

• epilepsy/tumor can be exception

  • slow to emerge/develop

• more control in non-human primate research

lesion study control groups

• methodological consideration

• compare subjects w lesions to demographically matched controls

  • compare performance on task

• hard to match all factors like psychoactive medication

  • control would have to also be taking x meds

• pts w complementary lesion profiles can serve as controls

  • seen often in memory science

  • have lesion in unrelated/diff part

selective hippocampus lesion

• hippocampus very sensitive and susceptible to oxygen deprivation, herpes, encephalitis

• loss of episodic memory and spatial navigation

• clean lesion of only hippocampus

• compared to hippocampus & medial temporal lobe cortex lesion

hippocampus and MTL cortex lesion

• lesion of hippocampus and medial temporal lobe which is close by

• loss of neocortical area as well

• compared w selective hippocampus lesion

task specificity

• methodological consideration

• no task that selectively reveals capacity of brain to support only ONE function

  • everything works in unison

• problem across neuro studies

• need various tasks to rule out other processes such as counting, color/shape perception

hemineglect

• everything on one side of body stops existing

• attention problem

• sxs most likely reflect functional breakdown at lvl of attentional networks rather than individual regions

network disruption

• disruption of harmonious activity

• stool example

  • can’t say specific leg is unique in x function

• system-wide dysfunction

disconnection syndrome

• occurs when higher-level cognitive functions are disrupted by damage to white matter tracts that link specialized, localized brain regions

• disorder not attributed to disruption of individual regions instead networks

etiology

• methodological consideration

• lesions confounded by features related to source of damage

• ex: ischemic stroke pts likely to have silent infarcts that cause cog deficits unrelated to study

  • only detectable post-mortem

• combat by having groups of pts w/ diff sources

  • in order to say deficit is not uniquely coupled to source but to loss of tissue

T1 MRI

• white matter is lighter/brighter

T2 weighted mri

• colors inverted so white matter appears dark

focal cortical dysplasia

• abnormal organization of cells in cerebral cortex

• neurons shaped wrong or wrong density

• irregular folding of gyri

• track ppl longitudinally

perinatal anoxia

• baby can’t breathe when being delivered

• brain is very sensitive and can cause small and irregularly shaped hippocampi

• 6 min = emergency

• causes developmental amnesia

  • no episodic mem, can’t remember past

  • but grow up normally (semantic knowledge not in hippocampus)

stroke

• sudden disruption of blood flow to brain

• ischemic = blocked

• hemorrhagic = rupture

  • artery rupturing causes blood to rush through and creates holes in brain

  • can blow out entire hemispheres

  • limits to claims we can make

infectious/metabolic disorders

• AIDS dementia - viral infection

• herpes simplex - viral infection

• korsakoff’s syndrome - nutritional deficiency/metabolic

• can cause lesions in brain

traumatic brain injury

• don’t affect all brain regions equally

• orbitofrontal regions more susceptible/affected bc skull is jagged and irregular above eye sockets

  • higher-order functions, pts appear child-like

diffuse axonal injury

• diffusion tensor imaging used to view white matter tracts

• from repeated, mild TBI (concussion) can lead to chronic neurodegeneration

• results from twisting and buckling forces that stretch and shear long axons in white matter deep inside brain

  • rest of neocortex looks fine

  • long-range connections disrupted

surgical resection

• very focal and selective

  • as little tissue as possible

• good premorbid data + can serve as own control

• tumor removal, epilepsy treatment or behavioral disorders

lesion overlap analysis

• no 2 ppl are identical

• look at individual anatomy and measure size of regions

• superimpose all subjects together and look for overlap

• hot spot is area attributed w loss of function (overlap maximal)

• not ideal but best way

compensation

• some w every injury; looking at how much and where

• cellular and systems lvl processes reorganize circuits at site of lesion

• additional recruitment of redundant or alternative pathways that might mask impairment

• longer since injury = more opp for rewiring

• slow tumor also permits more change

  • etiological differences important to consider

chronic v transient lesions

• can come to diff conclusions depending on data

chronic lesion

• opportunities for compensation that can mask impairment

  • neuroplasticity

• surgical resection

• can appear as if lesion of area does not affect performance

transient lesion

• temp shut off parts of brain during experiment

  • chemically or electrically and measure behavior immediately after

• no opportunity for compensation

• even tho region may appear irrelevant to task, compromises ability of the supposed relevant region

  • looks diff in chronic

single dissociation

• lesioning one area shows low performance in one task and not in other compared to control

• can’t draw conclusion—can be due to other reasons like severity or task at hand

double dissociation

• used to determine if 2 functions are independent in brain

• lesion 2 diff areas and see that performance goes down for different task compared to control

• ex: lesion hippocampus and see low performance episodic but high for semantic. lesion temporal pole and see high performance episodic and low for semantic.

transcranial magnetic stimulation

• form of transient lesions

• non invasive technique in healthy human subjects

• generates pulsed magnetic fields using electromagnetic coil on surface of head guided by knowledge of personal anatomy

• mag field induces electrical field that temp alters brain activity

  • can inc or dec excitability of targeted neurons

• penetrates skull w high spatial fidelity unlike scattering of eeg

  • target stimulation is possible

  • not useful for stimulating medial and ventral surfaces or subcortical regions like hippocampus

lesion-based brain mapping

• revealed deficits specific to certain brain regions

• supports modular brain

timeline of modular v distributed

• Gall’s phrenology suggested modular mind in modular brain

• flouren’s aggregate field theory suggested faculties of mind are distributed throughout brain

  • lesioned pigeon and rabbit brains and found focal lesions had no apparent impact

• modular brain resurrected w Broca and Wernicke aphasia showing what one area can do another can’t

• distributed back w/ Lashley’s law of action

  • tried to find engrams by training rats then lesioning. didn’t find difference in location only size of lesion

  • proposed all brain regions contribute equally to all cognitive functions

• modular back w Penfield’s epilepsy treatment

  • all pts experiencing same sxs in same regions

• lesion-based brain mapping declared modular brain winner

  • different brain regions support diff kinds of memory

  • HM bilateral hippocampus removal; procedural mem intact, episodic gone