10 - fMRI preprocessing and single subject stats Flashcards

1
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Question 1: Anatomical and Functional MRI
1. Explain the difference between anatomical MR data and fMRI data in terms of spatial resolution. How does the voxel size impact the quality of fMRI data?
2. Describe the difference between passive and active tasks in fMRI experiments. Give an example of each type of task.
3. Why is a flashing checkerboard often used as a stimulus in fMRI experiments? How does this stimulus lead to activation in the visual cortex?

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Question 1: Anatomical and Functional MRI
Anatomical MR data provides high-resolution images that depict the structural anatomy of the brain, whereas fMRI data provides lower-resolution images that capture changes in brain activity. The voxel size in fMRI is larger, leading to a rougher image. The voxel size impacts fMRI data quality, as smaller voxels can provide better spatial resolution, allowing for more precise localization of brain activity.
Passive tasks in fMRI experiments involve subjects not actively performing any actions. An example is observing a sequence of images. Active tasks require subjects to engage in specific activities, like pressing a button when seeing a certain image. A passive task may induce less neural activity compared to an active task.
A flashing checkerboard is a common stimulus in fMRI experiments because it generates substantial activation in the visual cortex. The flashing checkerboard produces alternating periods of visual stimulation and baseline fixation. Each tick mark indicates an image acquisition, allowing measurement of brain activity changes in response to the stimulus.

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2
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Question 2: Hemodynamic Response and Predicted Response
1. Detail the physiological changes that occur in response to neural activity, leading to the hemodynamic response. How does neurovascular coupling contribute to this response?
2. Explain the concept of the predicted response in fMRI analysis. How is the hemodynamic response function (HRF) used to generate the predicted response?
3. Discuss the purpose of convolving the HRF with the predicted neural activity. Why is the predicted response typically delayed and smoothed compared to the actual neural activity?

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Question 2: Hemodynamic Response and Predicted Response
Neurons firing require oxygen, which leads to hemoglobin changes from oxygenated to deoxygenated states. Neurovascular coupling triggers an oversupply of fresh blood, resulting in increased cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen consumption (CMRO2). These changes contribute to the BOLD signal, making fMRI sensitive to hemodynamic responses.
The predicted response combines the hemodynamic response function (HRF) with the predicted neural activity. By convolving the HRF with predicted neural activity, a smoothed and delayed version of the predicted response is obtained. This predicted response represents how neural activity translates into the observed hemodynamic changes captured by fMRI.
In fMRI analysis, the goal is to model the actual activity of brain regions relative to the predicted response. The generalized linear model (GLM) is commonly used for this purpose. The t-statistic measures how well a voxel’s response matches the predicted response, indicating activation. Activation maps are generated by thresholding these t-statistics.

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3
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Question 3: Preprocessing Steps in fMRI
1. Outline the main preprocessing steps involved in preparing fMRI data for analysis. Briefly describe the purpose of each step.
2. Motion correction is an essential preprocessing step in fMRI. Explain why motion correction is important, especially in the context of detecting small BOLD signal changes.
3. Describe the challenges associated with slice timing differences during image acquisition. How does slice timing correction help improve data quality?

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The main preprocessing steps in fMRI data preparation are:
Image reconstruction
Motion correction
Slice timing correction
Spatial filtering
Temporal filtering
Global intensity normalization
Motion correction is crucial to detect small BOLD signal changes amid motion-induced fluctuations. It realigns fMRI volumes to a common reference, compensating for both gross and subtle motion effects.
Slice timing correction addresses timing differences in slice acquisition. Because slices are acquired at slightly different times, this correction aligns the data by shifting and resampling voxel intensities. Proper order consideration is essential for effective correction.

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4
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Question 4: Spatial and Temporal Filtering
1. What is the purpose of spatial filtering in fMRI data preprocessing? Explain how spatial filtering can enhance signal-to-noise ratio and why it’s important for activation detection.
2. Define temporal filtering and discuss its role in fMRI data preprocessing. How does temporal filtering address the presence of low-frequency drifts and high-frequency noise in voxel time series?
3. Explain the concept of temporal autocorrelation in dense single-event models. Why is pre-whitening used to estimate autocorrelation, and how does it affect filtering choices?

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Question 4: Spatial and Temporal Filtering
Spatial filtering enhances fMRI data by increasing the signal-to-noise ratio when blurring is smaller than the size of activation. This concept is based on matched filter theory. Proper smoothing size balances noise reduction and preservation of small activation areas.
Temporal filtering deals with the removal of low-frequency drifts and high-frequency noise from voxel time series. Highpass filters eliminate drifts, while lowpass filters remove high-frequency noise. Bandpass filters combine both, but dense single-event models require pre-whitening for autocorrelation estimation.
Temporal autocorrelation arises in dense single-event models due to correlated fMRI activation over time. Pre-whitening is used to estimate autocorrelation and avoids lowpass filtering, which is essential to preserve high-frequency information.

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5
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Question 5: Motion Correction and Slice Timing Correction
1. Why is motion correction necessary in fMRI analysis? Describe the types of motion that can affect fMRI data and their potential impact on the results.
2. Compare and contrast the strategies for motion correction and slice timing correction. Discuss their respective effects on data quality and interpretation.
3. When dealing with motion correction and slice timing correction, what challenges arise if the order of these corrections is not carefully considered? Provide insights into the optimal order of applying these corrections and the potential consequences of a poor order choice.

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Question 5: Motion Correction and Slice Timing Correction
Motion correction is necessary in fMRI analysis to compensate for both voluntary and involuntary head movements. Even small motions can lead to significant signal changes that exceed the BOLD signal changes of interest.
Motion correction involves aligning fMRI volumes to a reference volume using rigid-body transformations. Slice timing correction addresses the variability in slice acquisition times, aligning voxel intensities to improve data quality. While there’s no strict order requirement, considering motion and slice timing corrections simultaneously minimizes potential confounds.
If motion correction is performed before slice timing correction and a voxel moves to a different slice, the timing correction can be affected. The correct order depends on the specifics of the study. Challenges include interpolation artifacts and other motion-related effects that can degrade functional results.

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6
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Question 6: Preprocessing Steps and Global Intensity Normalization
Explain the concept of global intensity normalization in the context of fMRI preprocessing. How does it differ from its origin in PET imaging? What is the purpose of scaling each dataset to the same value in 4D normalization?

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Question 6: Preprocessing Steps and Global Intensity Normalization
Global intensity normalization is a preprocessing step in fMRI that originates from PET imaging. It addresses variations in mean intensity between subjects and sessions due to factors like caffeine levels and scanner differences. In fMRI, it ensures that the mean intensity change over the entire experiment is consistent. This normalization scales each dataset to the same value, aiming for a constant mean intensity. This process is referred to as 4D normalization.

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7
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Question 7: GLM and Single-Subject Statistics
In the context of fMRI analysis, how does the General Linear Model (GLM) work? Describe the role of the design matrix and parameter estimates (β) in this framework. How are contrasts used to infer statistical significance of brain activity?

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Question 7: GLM and Single-Subject Statistics
The General Linear Model (GLM) is a framework used in fMRI analysis. It involves creating a design matrix that incorporates information about experimental conditions, stimuli, and other factors. The GLM estimates parameters (β) that represent the relationship between the design matrix and the observed data. Contrasts are then formed to infer statistical significance of specific effects. This process yields t-statistics that indicate the strength of the effect and associated p-values that determine significance.

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8
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Question 8: Autocorrelation and Noise Correction
Describe the challenges posed by autocorrelation in fMRI data. How does autocorrelation impact the estimation of parameter values? Explain the concept of pre-whitening in correcting for autocorrelated noise and its application in fMRI data analysis.

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Question 8: Autocorrelation and Noise Correction
Autocorrelation is a property of fMRI data where observations are correlated over time due to the slow nature of the hemodynamic response. Autocorrelated noise can bias parameter estimates. Pre-whitening involves estimating the autocorrelation of the residuals, constructing a filter to undo this autocorrelation, and applying the filter to both the data and the design matrix. This process helps in obtaining more accurate parameter estimates and valid statistical tests.

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9
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Question 9: Thresholding and Multiple Comparison Correction
Explain the multiple comparison problem in the context of fMRI analysis. What is the Bonferroni correction, and how does it address this problem? Compare the Bonferroni correction to the use of Random Field Theory (RFT) in controlling false positives.

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Question 9: Thresholding and Multiple Comparison Correction
The multiple comparison problem arises when testing hypotheses across many voxels. Bonferroni correction involves dividing the desired significance level (alpha) by the number of comparisons to control the familywise error rate. Random Field Theory (RFT) is a more sophisticated approach that considers spatial correlations among neighboring voxels. It defines clusters of significant voxels and uses cluster-based thresholds to control false positives more effectively.

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10
Q

Question 10: t-Contrasts and f-Contrasts
Differentiate between t-contrasts and f-contrasts in the context of fMRI analysis. How are t-contrasts used to test hypotheses about individual parameters, while f-contrasts are employed to address broader questions? Provide examples of scenarios where each type of contrast is useful.

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Question 10: t-Contrasts and f-Contrasts 5. t-Contrasts are used to test hypotheses about individual parameter estimates (β) derived from the GLM. They assess whether specific effects are significantly different from zero. f-Contrasts, on the other hand, address broader questions and involve combinations of parameter estimates. They test whether certain combinations of effects are significant, allowing for more complex comparisons.

T-Contrasts and F-Contrasts in fMRI Analysis:

T-Contrasts:
T-contrasts in fMRI analysis are used to test specific hypotheses about individual parameters or conditions within a statistical model. They focus on comparing the means of specific conditions or factors to determine if there are significant differences. T-contrasts generate t-statistic values, which indicate the strength and direction of the effect being tested. These contrasts are particularly suitable for addressing specific and targeted questions within an experiment.

F-Contrasts:
F-contrasts in fMRI analysis are employed to address broader questions by comparing multiple conditions simultaneously. These contrasts are designed to test hypotheses involving combinations of parameters or conditions, allowing for a more comprehensive assessment of the overall model. F-contrasts produce F-statistic values that indicate whether any of the included conditions have a significant effect on the data.

Examples of Usage:

T-Contrasts:
Imagine an fMRI study investigating the effects of a new drug on brain activity. Researchers could use a t-contrast to compare the brain activation levels between a control group and a group that received the drug during a specific task. This t-contrast would assess if there is a significant difference in brain activation between the two groups, pinpointing the specific regions that show significant changes.

F-Contrasts:
Consider an fMRI study examining the effects of different cognitive tasks on brain activation. Instead of focusing on individual tasks, researchers could use an F-contrast to examine if any of the tasks overall have a significant impact on brain activity. This broader contrast would provide insights into whether at least one of the tasks differs from the rest in terms of brain activation patterns.

In summary, t-contrasts in fMRI analysis are utilized to test specific hypotheses about individual parameters or conditions, while f-contrasts address broader questions by comparing combinations of conditions. T-contrasts are ideal for targeted investigations, while f-contrasts offer a more comprehensive assessment of overall model effects.

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11
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Question 11: Spatial and Temporal Filtering
Discuss the importance of spatial and temporal filtering in fMRI preprocessing. Explain the roles of high-pass and low-pass filtering in removing noise and preserving information. How do these filtering techniques relate to autocorrelation modeling?

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Question 11: Spatial and Temporal Filtering
Spatial filtering involves smoothing fMRI data to improve signal-to-noise ratio (SNR) and account for local variations. Temporal filtering includes high-pass and low-pass filtering. High-pass filtering removes low-frequency noise, preserving fine details, and enabling accurate autocorrelation modeling. Low-pass filtering is generally avoided as it interferes with autocorrelation estimation. Filtering is essential for noise reduction and maintaining the integrity of the data.

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12
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Question 12: Effect of Motion on fMRI Data
Describe the impact of motion on fMRI data quality and analysis. Why is motion correction crucial, and what are the potential consequences of not correcting for motion? How does motion affect both anatomical and functional aspects of fMRI scans?

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Question 12: Effect of Motion on fMRI Data
Motion in fMRI data can lead to distorted images and compromised analysis results. Motion correction is crucial to align images across time points and mitigate motion-related artifacts. Without motion correction, significant false positives and reduced sensitivity can occur, impacting both anatomical and functional aspects of fMRI scans.

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13
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Question 13: Design Matrix and GLM Estimation
How does the design matrix play a fundamental role in fMRI analysis using the General Linear Model (GLM)? Explain how the design matrix incorporates information about experimental conditions, stimuli, and other factors. What are parameter estimates, and how are they estimated using the GLM?

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Question 13: Design Matrix and GLM Estimation
The design matrix summarizes experimental information such as stimulus timings and conditions. In the GLM framework, parameter estimates (β) are estimated by fitting the design matrix to the observed data. Each β corresponds to the contribution of a particular condition or effect. Contrasts are formed by combining these β values to test specific hypotheses, producing t-statistics that indicate the significance of the effects.

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14
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Question 14: Neural Hemodynamics and Hemodynamic Response
Describe the relationship between neural activity and hemodynamic response in fMRI studies. How does neurovascular coupling lead to changes in cerebral blood flow and the BOLD signal? What is the significance of the hemodynamic response function (HRF) in fMRI analysis?

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Question 14: Neural Hemodynamics and Hemodynamic Response
Neural hemodynamics refers to the coupling between neural activity and changes in blood flow and oxygenation levels. Neurovascular coupling leads to the hemodynamic response, a delayed and prolonged response to neural activity changes. This response results in the Blood-Oxygen-Level Dependent (BOLD) signal measured in fMRI, which indirectly reflects neural activity.

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15
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Question 15: Preprocessing Steps and Noise Reduction
List and briefly explain the key preprocessing steps involved in fMRI data preparation. How does each step contribute to noise reduction and improving the quality of the fMRI data? Discuss the purpose of spatial smoothing and temporal filtering in this context.

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Question 15: Preprocessing Steps and Noise Reduction
Key preprocessing steps in fMRI include global intensity normalization, motion correction, reconstruction, slice timing correction, spatial smoothing, and temporal filtering. Global intensity normalization equalizes mean intensity across datasets. Motion correction aligns images to correct for motion artifacts. Reconstruction creates images and removes artifacts. Slice timing correction aligns slices within volumes. Spatial smoothing improves SNR, and temporal filtering reduces noise while preserving relevant frequencies.

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