fmri analysis of functional brain connectivity in three
TRANSCRIPT
fMRI analysis of functional brain connectivity in three language tasks in
schizophrenia
1
1Department of Physics and Astronomy, University of British Columbia6224 Agricultural Road, Vancouver, British Columbia, Canada, V6T 1Z1
1
Acknowledgements:
OUTLINE
1. Motivation2. Theory3. Experiment Details4. Resources5. Summary
2
1.1 Overview of schizophrenia and current treatment options
POSITIVEHallucinations
Delusions
DISORGANIZEDDisorganized affect &
speech
NEGATIVEPoverty of Speech
Flat Affect
SYMPTOMS
3
COGNITIVEImpaired memory,
attention & executive function
1.1 Overview of schizophrenia and current treatment options
● Treatment Options
○ Pharmaceuticals
■ Typical & Atypical
Antipsychotics
■ Side effects, moderate
efficacy & resistance
4https://www.psycom.net/clozaril-clozapine
1.1 Overview of schizophrenia and current treatment options
● Treatment Options
○ Cognitive Therapy
■ Cognitive Behavioural Therapy (CBT)
■ Metacognitive Training (MCT)
■ Moderate efficacy
5
1.1 Overview of schizophrenia and current treatment options
Adjunct & Improved
Treatments
● Ex. Neuromodulation
Pharmaceuticals
● Side effects● Limited efficacy● Resistance
Cognitive Therapy
● Limited efficacy
6
1.2 Neuromodulation
● Neurons & Brain Networks
○ Neurons = nervous system cells
○ Communicate by releasing
neurotransmitters upon electrical
impulses
7https://www.neuroscientificallychallenged.com/glossary/neuron/Neuron
1.2 Neuromodulation
● Neurons & Brain Networks
○ Found in networks
throughout brain
○ Brain network activity can
change
8https://www.studzine.com/brain-artificial-intelligence-neural-networks/
9Auditory Language Default
ModeInternal
AttentionResponse
1.2 Neuromodulation
● Neuromodulation
○ Modify neural oscillatory electrical signals to increase or
decrease the likelihood of neuron activation
○ Transcranial Alternating Current Stimulation
10http://www.medicalexpo.com/prod/electrical-geodesics/product-68326-544197.html
1.3 Contribution of fMRI
● Neuromodulation
○ Requires spatial and temporal resolution
11
Lorem ipsum Dolor nec
1 Lorem ipsum dolor sit amet nec at adipiscing2 Lorem ipsum dolor sit amet nec at adipiscing3
fMRI EEG3-5 mm cm1 SPATIAL
1-3 s ms2 TEMPORAL
BOLD signal
Neuron firing
patterns3 USEFUL TO
MEASURE
1.3 Contribution of fMRI
BOLD Signal = Blood Oxygenation Level Dependent Signal
12Glover, G. H. (2011). Overview of Functional Magnetic Resonance Imaging
1.3 Contribution of fMRI
● Neuromodulation
○ Requires spatial and temporal resolution
13
Lorem ipsum Dolor nec
1 Lorem ipsum dolor sit amet nec at adipiscing2 Lorem ipsum dolor sit amet nec at adipiscing3
fMRI EEG3-5 mm cm1 SPATIAL
1-3 s ms2 TEMPORAL
BOLD signal
Neuron firing
patterns3 USEFUL TO
MEASURE
THEORY
2. Theory1. Functional Magnetic Resonance Imaging (fMRI)2. BOLD Signal3. fMRI-Constrained Principal Component Analysis
(fMRI-CPCA)
14
2.1 fMRI
● Nuclear Magnetic Resonance
○ Magnetic moment of protons from
H nuclei in water
○ Tip away from B0
○ Precession frequency: 𝟂 = 𝞬 B0
15https://my-ms.org/mri_physics.htm
16
T2: Transverse component dephasing
T2*: Reversible dephasing due to field inhomogeneities
T1: Longitudinal component recovery
https://www.researchgate.net/figure/Schematic-of-T1-and-T2-relaxation-MRI-utilises-the-behaviour-of-protons-within-varying_fig2_227712215
2.1 fMRI
RF
B0
B0
2.1 fMRI
● Signal Localization
○ RF pulse selects slice
○ Frequency & Phase encoding
gradients localize within slice
17http://mriquestions.com/slice-selective-excitation.html
2.1 fMRI
● Echo Planar Imaging
18http://mriquestions.com/echo-planar-imaging.html
2.2 BOLD Signal
19
Oxyhemoglobin = Diamagnetic
↓ magnetic susceptibility
↑ T2*
↑ Intensity
Deoxyhemoglobin = Paramagnetic
↑ magnetic susceptibility
↓ T2*
↓ Intensity
2.3 fMRI-CPCA
● fMRI-CPCA
○ Determine functional brain networks
○ Estimate post-stimulus BOLD signal changes
○ Test effects of experimental manipulations
20
2.3 fMRI-CPCA
21
ZInputData
GCConstrainedVariance
EResidualVariance
UComponent
Scores
DSingularValues
V’RightSingular
Vectors
GDesignMatrix
PPredictorWeights
Principal Component Analysis
Plot against time
Component Loadings:
VD/√(m-1)
Multivariate Least-squares Linear Regression
Regression
2.3 fMRI-CPCA
● Z Activation Matrix
22
Raw Preprocessed
2.3 fMRI-CPCA
● G Design Matrix
○ Encodes task timing
○ Scans X Conditions at post-stimulus time
○ Finite Impulse Response model
○ Expected signal: 1
○ Otherwise: 0
23
GDesignMatrix
2.3 fMRI-CPCA
● Z matrix regressed onto G matrix with multivariate least-squares linear regression
24
2.3 fMRI-CPCA
● Principal Component Analysis extracts components from GC
25
VOXELS
SCAN
S
GCVariance
constrainedbyFIRmodel
ULeftSingularVectors
DSingularValues
V’RightSingular
Vectors
Component Scores
2.3 fMRI-CPCA
● Columns represent component loadings, or anatomical correlates of each brain network
26
DSingularValues
VRightSingular
Vectors
√(m-1)
Component Loadings
2.3 fMRI-CPCA
● Predictor weights indicate importance of each column in G for a given component
27
UComponent
Scores
GDesignMatrix
PPredictorWeights
2.3 fMRI-CPCA
● Predictor weights plotted against time give the hemodynamicresponse (HDR) for the component
28
PPredictorWeights
2.3 fMRI-CPCA
29
ZInputData
GCConstrainedVariance
EResidualVariance
UComponent
Scores
DSingularValues
V’RightSingular
Vectors
GDesignMatrix
PPredictorWeights
Principal Component Analysis
Plot against time
Component Loadings:
VD/√(m-1)
Multivariate Least-squares Linear Regression
Regression
Experiment Details
3. Experiment Details1. Language Tasks2. Functional Brain Networks3. Procedure
30
3.1 Language Tasks
Metrical Stress
(MS)
31Headache
3 sec
2 sec
+
Breakfast
+3 sec
2 sec
3.1 Language Tasks
Thought Generating
Task
(TGT) 32Instructions
ITI: Visual Distractor
ITI: Visual Distractor
5 sec
15 sec
6 sec
5 sec
2 sec
Camera
“something you…”
Table
“something you…”
3.1 Language Tasks
Semantic Association
(SA)33
3.3 Procedure
34
1
fMRI Scan Preprocessing
SPM8
Networks & HDR
fMRI-CPCA
2
Statistical Analysis
SPSS Repeated measures ANOVAs
3
Network Classification
Templates HDR
4
4. Resources
● Access to MS, TGT and SA datasets
● SPM 8 Software
● fMRI-CPCA Software
● SPSS Software
● Computer time
35
5. Summary
● fMRI may be used to examine BOLD signal
● Determine functional networks from three language tasks in both healthycontrols and schizophrenia patients with fMRI-CPCA
● Increase understanding of spatial localization of brain networks and influencepotential neuromodulation methods for schizophrenia patients
36