Fundamental-Neuroscience-for-Neuroimaging

https://www.coursera.org/learn/neuroscience-neuroimaging/home/welcome

Anatomy

• Neurons 神经元细胞
  • 
  • Axon: transmits electrical signal 轴突
  • axon terminal: = presynaptic terminal, end on adjoining dendrites or cell body
  • Dendrites: receives contact 树突
• Glia 神经胶质细胞
  • majority of cells
  • function
    • connective tissue
    • metabolic support roles
    • remove excessive secretions
    • produces myelin=insulates neurons
• Structural anatomy
  • cytoarchitectural organization
  • dissociable brain structure
  • dissociable brain networks
  • rudimental classification
• vascular anatomy
  • 
  • circle of willis: blood enter brain
    • anterior cerebral artery
  • 
• Similarity with other animals
  • similar structure, human just bigger cortex
  • allows experiment on simpler animals
• development stages
  • cortex last
  • 

Terminology

-axis

• Rostrum 嘴 cauda 尾

• dorsal 背 ventrum 腹

  

• human

  

  • superior - inferior
  • antirior - posterior
  • medial - lateral

• planes

  

  • in MRI

    • coronal = frontal
    • axial - transverse
    • sagittal

    

    • left vs right in frontal view

      • radiological convention: left on right side of image
        • face forward
      • neurological convention: left is left in image
        • face backward

    • use fiduciary marker - right side

      

• proximal 近vs distal

• ipsilateral 同側vs contralateral 異側

Methods of Communication in the Brain

• reticular 网状 theory (Golgi)

  • connected reticular net

• neuron doctrine

  • neurons are independent, contigual not continual

• types:

  • sensory neuron - external stimuli -> electrical signals
  • interneuron - processing & relay
  • motor neuron - electrical signals-> muscle or gland movement

• ion channels & ion pumps

  • 
  1. influx of Ca++ -> synaptic vesicles fuse with pre-synaptic membrane
  2. transmitter released into cleft
  3. transmitter binds receptor molecules on post-synaptic membrane
  4. post-synaptic channels then open/close based on binding
  5. opneing -> influx of ions (Na+/K+) / close -> prevents
  6. causes either depolarize or hyper-polarize
  7. if post-synaptic voltage large enough -> electrochemical pual is generated = action potential
  8. simultaneously
     • action potential travels down axon.
     • used vesicle is retrieved and recycled
  9. new transmitter is synthesized
  • 
  • Excitatory post-synaptic potential (EPSP)
    • sometimes sum of EPSPs from multiple neuros are necessary for action potential
      
  • recording
    • 
    • inside neuron (1)
    • outside neuron (2)
      • extracellular eletrode can only measure local neuronal environment (local field potential LFP)

• different neurotransmitters (>50)

  • by makeup
    • amino acids
      • glutamate
      • aspartate
      • glycine ...
    • peptides
      • somatostatin ...
    • others
      • Serotonin 血清素
      • Histamine 组胺
      • Melatonin 褪黑素
      • Norepinephrine 去甲肾上腺素
  • by excitatory vs inhibooary
    • excitatory
      • epinephrine 肾上腺素
      • norepinephrine
    • inhibitory
      • serotonin
      • GABA
    • both
      • dopamine
  • important examples
    • acetylcholine 乙酰胆碱
      • excitatory
      • activates motor neurons
      • attention, arounsal, learning, memory
      • low levels in Alzheimers
    • dopamine
      • fine movements
      • positive emotions
      • abnorally low levels in Parkinsons
      • abnorally high in frontal areas of schizophrenia
    • glutamate 穀氨酸
      • most commonly found
      • learning & memory
      • execessive production is toxic (ALS)
      • binds to AMPA, open, allow Na+ in
      • binds to NMDA, open, allow Ca++ in
      • 
  • different receptor react to different neurotransmitters
    • 
    • agonist 激动剂
    • competitive antagonist - blocks other agonist from binding
    • non-competitive antagonist - different site

• interaction with body

  • direct innvervation through spinal cord + peripheral nerve system

    • cranial nerves

      

    • corticospinal tracts

      

  • through hormones in vascular system
    • brain is neurochemically protected by BBB blood-brain barrier
      • 
      • endothelial cells line blood vessels
      • needed material is actively transported, like glucose
      • only small hydrophobic molecules e.g. O2 are allowed through
      • prevents toxins, bacateria, etc.
    • parts not protected by BBB：
      • hypothalamus 下丘脑
      • pituitary 脑下垂体
      • pineal glands 松果体
      • regulates temperature, thirst, hunger, circadian rhythm, sleep, stress response, etc.
    • bi-directional
      • e.g. adrenaline/epinephrine
        • through blood, activates sympathetic nervous system 交感神经: fight/flight responses
        • binds to receptors on vagal nerve -> releases glutamate -> encode the event to remember for future

Functional anatomy

• cerebrospinal fluid CSF 脑脊液

  • protects brain and spinal cord from trauma
  • supply nutrients

• grey matter

  • contains neuronal cell bodies
  • info processing

• white matter

  • fiber bundles of axon projects
  • information transmission

• primary motor cortex

  • dorsal portion of frontal lobe
  • plan movements
  • send long axons down spinal cord
  • 

• primary somatosensory cortex

  • receives sensory input
  • 
  • amount of cortex is proportional to density of tactile receptors

• thalamus 丘脑

  • relay sensory and motor signal
  • regulation of sleep and consciousness

• visual cortex

  • orientation
    • 
  • what or where pathway
    • 

• cerebellum 小脑

  • seperate structure
  • receive from sensory, spinal
  • coordinates posture, balance, timing coordination

• Organization of Cognitive Domains

  • language
    • Broca's aphasia
      • 
      • understand words and simple sentences
      • know what they want to say
      • unable to generate fluent speech
    • Wernicke area - silent, writing
      • receptive aphasia
      • unable to comprehend. can express
    • 
  • Gage 1848 accident
    • speech/motor still functions
    • severe personality change
  • memory
    • patient H.M.
      • removed bilateral hippocampus 海马体, amygdala 杏仁体 and surrounding cortext to fix seizure
      • intact language, IQ, working memory and motor control
      • unable to learn new facts/events
      • unable to remember anything since the surgery
      • but he's able to improve some motor skills (draw star) but don't consciously remember -> must be multiple area
    • multiple systems
      • medial temporal lobe
      • basal ganglia 基底核
        • fine motor planning and movements
        • stratum: reward, reinforcement
        • motor learning, stimulus response learning
        • 
  • specific tasks
    • fusiform face area - recognizing faces

Neuropsychological Assessment of Cognition

Neuropsychology: behavioral expression of brain function

• cognition

  • initially: single function of intelligence. IQ=100 is median

• emotionality

• executive

• Screening testing

  • RBANS
  • MMSE
  • MOCA

• Hypothesis testing

• Neuropsychological battery approach

• comprehensive

Example

• memory assessment
  • Wechsler memory scale
    • personal and current info
    • orientation
    • mental control
    • logical memory
    • digit span
    • visual repro
    • paired associate
  • word list learning
• Executive
  • volition
  • planning
  • purposive action
  • effective performance
  • e.g. Stroop word test - word "red" colored in blue

Approaches to Neuroimaging

• Categories
  • structural
    • anatomy
    • pathology
  • functional
    • metabolic
    • pharmacologic
    • cognitive
• techniques

  • EEG

    • measure activity through electrodes on scalp

  • CT - computed axial tomography

    • series of xrays
    • many cross sections rescontructed to a 3D volume
    • fast, but moderate radiation

  • single photoon emission computed tomograph - SPECT 单光子发射计算机断层成像术

    • gamma emitter tracer through 静脉注射
    • spacial resolution not good - a few cm

  • PET - positron emission tomography

    • positron emitting radionuclide that binds to biologically active molecule
      • FDG-PET: marker for glucose uptake (tumors, Alzheimers)
      • 18F-AV-45 PET market for beta amyloid (protein occursi in Alzheimer's)
    • detects pairs of gamma rays
    • higher resolution than SPECT

  • MRI

    • static + variable 磁场 perturb H atoms
    • resulting resonance is masured by radio frequency receivers
    • different pulse sequence -> different contrast for tissue type
    • magnetic field is 60x stronger than earth
      • ppl w pace maker should never do MRI
      • dangerous to ave metallic objects in vicinity
    • no radiation/known side effects
    • high resolution

    

    • -270C super conducting metal
    • additional head antenae

  • fMRI

    • magnetic resonance from oxygenated vs non-oxygenated blood

  • diffusion tensor imagining

    • refined application of MRI
    • measures directionality of water molecules
    • assess fiber projecttions & white matter integrity

  • spectroscopy

    • refined application of MRI
    • magnetic signatures of various metabolites

Basics of MRI

• MRI signal
  • spin both its own axis and the magnetic field
    • parallel: low energy
    • anti-parallel: high energy
  • after a few seconds, reach equilibrium, all protons are aligned
  • static field can't be measured. MRI signal introduces different direction perpendicular to the main field, causes protons to move away from axis
    • when stops, procession back to original alignment
    • t1 & t2 plane
      • t1: longitutional (original field position)
      • t2: transverse
    • the procession induces a signal in receiver coil
    • relaxation time: time it takes to recover after being disturbed
    • different biological matter have different but consistent t1 and t2 relaxation times
      • tumor also different
    • 
  • spatial specificity
    • Larmor frequency frequeny needed to changea spin from low to high energy spin
      • MRI mostly targeting water molecules
    • Larmor frequency depends on local magnetic strength
    • create bands of frequency/magnetic gradient
    • put together:
      • linear gradients create sptial specificity
      • radio purlse selectively excites slices
• fMRI
  • 
  • oxygenated hemoglobin vs de-O hemoglobin have different effects on dephasing - de-O hemoglobin cause more dephasing
  • Blood Oxygen Level Dependent (BOLD) MRI
  • measure changes in homogeneity in magnetic field (T2*)
    • T2: transverse magnetization decay of a spin after radio frequency pulse
    • T2*: transverse magnetization decay from local magnetic field variations
    • 
    • de-O hemoglobin: paramagnetic, introduces inhomogeneity
    • O hemoglobin: little effect
  • BOLD signal:
    • HRF: hemodynamic response function
      
    • it doesn't measure neural activity directly
    • measures metabolic demands
  • physiological basis:
    1. glutamate releases
    2. open post-synaptic ion channels
    3. re-uptake of glutamate by astrocyte triggers glucose metabolism
    4. astrocytes pump out ions to restor ionic gradients
    5. processes use glucose + O2
    • MUA- multi-unit activity
    • LFP local field potential = summation of post-synaptic potential more correlated (but delayed) w BOLD activity

MRI studies

• structural

  • qualitative eval

    • 

  • volumetric analysis:

    • count voxels -> difference of volume of various parts compared to controls
    • automatic segmentation

  • analyze cortical thickness

  • strutural morphology: compare shape differences

  • example of correlating behavioral w structual analysis:

    • Aerobic Exercise Training Increases Brain Volume in Aging Humans

  • many reasons for structural brain changes:

    • development/atrophy
    • exercise
    • substance use
    • inflammation / edema
    • gliosis

• fMRI studies

  • spatial resolution: 1-1.5 mm
  • temperal resolution ~0.5 sec
  • no long lasting effects
  • block of epoch design
    • repetitive on and off time
    • simple to design, robust activation due to large number of trials
    • con：
      • assume single mode of activiation at consistant level over repititions
  • event related design
    • pro:
      • flexible analysis
    • con:
      • reduced detection power
      • sensitive errors in hemodynmaic response function
  • cognitive subtraction
    • assumption: different cognitive components are additive
    • subtract activitation of control task from that of experiment task can isolate effects of that difference in task (taskA-taskB)
    • subtraction is only valid if condition differs in only one property
      • e.g. using resting condition as control is bad
      • When zero is not zero: the problem of ambiguous baseline conditions in fMRI
      • find face recognition

Experimental design

technical limitation

• limited visual field + response options
• scanner drift - each runs limit to 4-6 min, then restart
  • longer will cause heat up, change accuracy
• subject motion: - mm movmement change will interfere psychological state

psychological state

• is the subject effectively engaged?
  • 
  • after subject answers, maybe mind drifts off to think about other things
• are they using shortcuts to solve the problem?
• how long does the psychological state last
• does the task induce unintended psych state?
  • e.g. get anxious or frustrated

statistical design

• substraction
• factorial
  • multiple factors & interaction
• parametic
  • increase levels of difficulty
• measure before/after intervention e.g. drug/training/therapy

Functional connectivity MRI

• Hebbian principle: cells fire together, wire together
• spatial correlation vs temporal correlations
• voxel to voxel connectivity
  • compare every voxel against every other
• seed based connectivity
  • pick an area, compare other areas with that
• independent componenet analysis
  • how many independent networks are at work?
    • DMN default mode network
      • highly correlated during wakeful rest
      • less active of external task
      • developmentally established:
        • more developed as kid grows up
      • overlap with structural connectivity
      • neurological basis of self, self-reference, theory of mind, social cognition
      • support comprehension, learning, memory
      • support thinking of past and future
      • deactivation of DMN correlate:
        • memory encoding
        • task difficulty
      • activiation of DMN after learning improves memory
      • connectivity in DMN observed in
        • alzheimer's
        • autism
        • depression
        • aging
        • schizophrenia
        • epilepsy
        • OCD
        • anoerexia nervosa ...

Diffusion Tensor Imaging

• Hydrogen

• unpaired proton -> magnetic properties, sutied to disturb the local static mag field

• unibiquitous - water & fat issue

• water diffusion:

  • isotropic: all directions
  • anisotropic: has dimensionality

• brain

  • grey matter - cell bodies- isotropic
  • white matter - axon - anisotropic

• DTI:

  • gradient pulses

    • cancel out for stationary H2O
    • lack of signal for diffusing molecules

  • for each voxel, find the eigenvalues for each eigenvector

  • probablistic fiber tracking

    

• studies

  • fractional anisotropy
    • 0: isotropic diffusion
    • 1: diffusion in 1 direction
    • measure
      • fiber density
      • white matter integrity
  • FA correlation with symptoms
    • e.g. OCD
  • DTI tracography in surgical planning
    • tumor removal planning
    • eletrode simulation

Magnetic Resonance Spectroscopy

• processions causes a small local magnetic field, opposite direction of static mag field

• change the local effective mag field, causes resonance frequency to shift "chemical shift"

  • value of the shift gives info about the molecular group of that nucleaus
  • MRS quantify local presence of certain chemical compounds

  

  • spectra can be obtained from different nuclei but H most common

• water signal must be suppressed

  • Chemical Shift Selective suppression pre-saturate water signal using spepcifc pulse frequency

• sepctra provide metabolite concentration in different area of brain

• common metabolite

  • NAA N-acetylaspartate
    • normally highest peak in normal brain
    • decrease <-> white matter disease, malignant neoplasms
  • Cr creatine
    • marker for energetic system and intracelluar metabolism
    • reduced siganal in tumors
  • Cho Choline
    • marker of celluar membrane turnover - cellular proliration
    • incrase in infarction梗塞/inflammation
  • LacLactate
    • marker of anerobic metabolism, e.g. cerebral hypoxia, ischemia, seizures, metabolic disorders,
    • occur in cysts, normal pressure hydrocephalus 腦積水, certain tumors

• clinally:

  • most used in brain tumors, metabolic disorders

book recommendations

• Principles of Neural science - Kandel, schwartz