fMRI analysis of functional brain connectivity in three language tasks in

schizophrenia

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1Department of Physics and Astronomy, University of British Columbia6224 Agricultural Road, Vancouver, British Columbia, Canada, V6T 1Z1

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Acknowledgements:

OUTLINE

1. Motivation2. Theory3. Experiment Details4. Resources5. Summary

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1.1 Overview of schizophrenia and current treatment options

POSITIVEHallucinations

Delusions

DISORGANIZEDDisorganized affect &

speech

NEGATIVEPoverty of Speech

Flat Affect

SYMPTOMS

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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

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1.1 Overview of schizophrenia and current treatment options

Adjunct & Improved

Treatments

● Ex. Neuromodulation

Pharmaceuticals

● Side effects● Limited efficacy● Resistance

Cognitive Therapy

● Limited efficacy

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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

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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

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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)

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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

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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

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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

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2.3 fMRI-CPCA

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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

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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

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GDesignMatrix

2.3 fMRI-CPCA

● Z matrix regressed onto G matrix with multivariate least-squares linear regression

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2.3 fMRI-CPCA

● Principal Component Analysis extracts components from GC

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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

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DSingularValues

VRightSingular

Vectors

√(m-1)

Component Loadings

2.3 fMRI-CPCA

● Predictor weights indicate importance of each column in G for a given component

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UComponent

Scores

GDesignMatrix

PPredictorWeights

2.3 fMRI-CPCA

● Predictor weights plotted against time give the hemodynamicresponse (HDR) for the component

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PPredictorWeights

2.3 fMRI-CPCA

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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

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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

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1

fMRI Scan Preprocessing

SPM8

Networks & HDR

fMRI-CPCA

2

Statistical Analysis

SPSS Repeated measures ANOVAs

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Network Classification

Templates HDR

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4. Resources

● Access to MS, TGT and SA datasets

● SPM 8 Software

● fMRI-CPCA Software

● SPSS Software

● Computer time

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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

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