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What is PPI analysis?

Published in Neuroimaging Analysis 4 mins read

PPI analysis, or Psychophysiological Interactions analysis, is a technique used in fMRI research to identify brain regions where activity changes in relation to the interaction between a psychological task and activity in another brain area. In simpler terms, it helps researchers understand how the relationship between different brain regions changes depending on what a person is doing.

Understanding the Core Concepts

PPI analysis helps answer questions like: "Does the connection between brain area A and brain area B change when someone is performing task X compared to when they are at rest?" This is different from simply identifying areas activated by a task; PPI focuses on how the relationship between areas is modulated by the task.

  • Psychological Variable: This refers to the experimental manipulation or task being performed (e.g., viewing emotional images, performing a memory task).

  • Physiological Variable: This is the activity in a specific brain region (often called the "seed region") whose influence on other brain regions is being investigated.

  • Interaction Term: This is the core of PPI. It's the product of the psychological and physiological variables, representing the change in the relationship between the seed region and other brain areas due to the task.

How PPI Analysis Works

The general steps involved in a PPI analysis are:

  1. Define a Seed Region: The researcher selects a brain region of interest (the "seed region") based on prior hypotheses or findings. This region's activity will be used to predict activity in other regions.

  2. Extract Seed Region Activity: The average fMRI time series is extracted from the seed region. This represents the physiological variable.

  3. Create the Psychological Regressor: A regressor representing the task or psychological variable is created. This is typically a vector indicating when the task was being performed.

  4. Calculate the Interaction Term: The interaction term is calculated by multiplying the seed region activity (physiological variable) by the task regressor (psychological variable). This term captures the modulation of the seed region's influence by the task.

  5. Perform a Regression Analysis: A general linear model (GLM) is used to regress the fMRI data in the whole brain against the psychological regressor, the physiological regressor, and, crucially, the interaction term.

  6. Interpret the Results: Brain regions showing a significant correlation with the interaction term are interpreted as regions whose connectivity with the seed region is modulated by the task.

Example Scenario

Imagine a study investigating how the amygdala (involved in emotion processing) influences visual cortex activity during the viewing of fearful faces.

  • Seed Region: Amygdala
  • Psychological Variable: Viewing fearful faces vs. neutral faces
  • PPI Analysis would reveal: Brain areas in the visual cortex that show increased connectivity with the amygdala specifically when viewing fearful faces (compared to neutral faces). This suggests that the amygdala's influence on visual processing is enhanced during emotional processing.

Key Considerations

  • Choice of Seed Region: The results of a PPI analysis are highly dependent on the choice of the seed region. Justification for this choice is crucial.

  • Interpretation: PPI results indicate task-dependent changes in functional connectivity, not necessarily direct anatomical connections. They suggest a context-dependent relationship, not a causal one.

  • Statistical Thresholding: Appropriate statistical thresholds must be used to correct for multiple comparisons, as PPI analyses often involve examining activity across the whole brain.

Advantages of PPI Analysis

  • Investigates task-dependent connectivity: PPI goes beyond simply identifying task-related activation; it reveals how interactions between brain regions change depending on the task.
  • Hypothesis-driven: The choice of a seed region makes PPI a hypothesis-driven approach, allowing researchers to test specific predictions about brain networks.

Limitations of PPI Analysis

  • Sensitivity to Seed Region Selection: Results depend heavily on the chosen seed region, potentially leading to biased interpretations.
  • Correlation vs. Causation: PPI analysis only demonstrates correlations and does not prove direct causal relationships between brain regions.
  • Complexity: Requires a solid understanding of GLM and fMRI data analysis techniques.

In conclusion, PPI analysis is a powerful tool for investigating task-related changes in functional connectivity, offering valuable insights into how brain regions interact to support cognitive processes.

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