Experimental Design!
Variables!! Independent Variables: variables hypothesized by the experimenter to cause changes in the measured variables.!! Conditions: Different values of the independent variables!! Dependent Variables: Quantities measured to evaluate the effects of the independent variable.!
Examples of Variables!! Hypothesis: Attention speeds up processing time.!! Independent Variables: Attentional status of a stimulus (2 conditions: attended or unattended)!! Dependent Variables:!! reaction time - RT is a continuous variable!! Answering in less than 500ms or more than 500ms (categorical variable)!
Categorical vs. continuous variables.!! Perception is often categorical!! Detection (yes/no)!! Discrimination (2 categories of stim)!! Ba/Pa continuum or color continuum!! Often simplify by making variables categorical (attended/unattended)!
Constructing research hypotheses! Hypothesis: Statement about the relationship between independent and dependent variable
! Hemodynamic H. : Questions about the BOLD response (shape and timing of BOLD response) as a function of blood physiology!! Neuronal H. : Link between neural activity and BOLD!! Psychological H. : Link between psychological state and BOLD!
Causal chains and epiphenomena! Coal in the engine necessary for locomotive move Coal in the engine leads to whistle noise Is whistle noise necessary for locomotive to move?
BOLD activity is not part of the causal chain of events, only a by-product of neural activity
Selecting appropriate control stimuli!! Brain regions specific to face processing!! What do you do?! Look for activation! to faces?!
Fourier transformed Phase scrambled Inverse FFT
Use other objects: interesting, are made of smaller nameable parts
Evidence for a face area in humans (from N. Kanwisher)
Questions to ask yourself when designing or evaluating a research study.!
Basic principles of blocked designs!! Hypothesis!! Listening to music improves studying!! Design!! Memory for lists of words with and without concurrent music!! Dependent variable!! Number of words recalled with and without music.!
Does listening to music improve studying?!! Is it a good design for looking at brain systems underlying this effect?!
Studies of Attention (Hillyard et al.)!
Task A: attend Left - left stim ATTENDED Task B: attend Right - left stim Unattended Task C: attend Left - right stim Unattended Task D: attend Right - right stim ATTENDED Attentional Effect Compare (Task A + Task D) versus (Task B + Task C) Attend Right vs Attend Left Task B+D versus A+C
Effects of attention on early visual cortex! Attentional modulation after target presentation! Early visual cortex activation is enhanced during processing of attended target!
Within-conditions variability much smaller than between-conditions variability in blocked fmri data.!
Effects of block interval on the fmri hemodynamic response.!
Effects of block interval on the fmri hemodynamic response.!! 2sec is getting too short to allow detectable changes. 8-12sec best - look out for signal drift when longer blocks!!
Insensitivity of blocked designs to the shape of the hemodynamic response.! Superposition of activation!
Even distorted HDR will lead to superposition...! Randomly scrambled HDR still reaches a plateau as stimuli are added! Cannot retrieve HDR from blocked paradigms!
Possible origins of increases and decreases observed in fmri! Need a baseline! But what is a good baseline?!
Oxygen Extraction Fraction (OEF) as a possible baseline for brain activity.!! OEF = ratio between cerebral metabolic rate for Oxygen and cerebral blood flow OR proportion of available O2 removed from the blood!! OEF decrease when neural activity due to greater increase in blood flow than metabolic rate (note: OEF and BOLD are inversely related)!
Oxygen extraction fraction (OEF) as a possible baseline for brain activity.! Cerebral Metabolic Rate for O2! OEF = CMRO2/CBF!
! Regions where activity decrease during experimental task (or increase at rest)!! Medial and lateral Parietal Cx!! DorsoMedial and VentroMedial Frontal Cx!! Hypothesis: Self-directed thought Gusnard and Raichle, 2001!! Respond to unexpected event - Novelty detector!! Assessment of reward for action - self monitoring!! Reflective thinking (DM Frontal Cx)!
Event-related fmri design.!! Variable ISI between 2 and 20sec!! Random order of condition!! Time locking to critical event and signal averaging!
Comparisons of blocked and eventrelated designs.!! Stem completion task:! Ora -> Orange!! Block: 30sec on (1 item/2sec) - 30 sec rest!! Event Related: 1 item every 15sec (TR of 2sec or 1sec)!
Comparisons of blocked and eventrelated designs.! Blocked has more power, but extremely good convergence!
Latency differences between brain regions!! No agreement on whether can use fmri signal to predict flow of information (causality)!
Not all designs can be blocked!! Some research questions require single event:!! what are the brain structures necessary for detecting unfrequent targets? P300 with generators in prefrontal, parietal and hippocampus!
..O O O O O O O X O O O O O O O O Task: Count number of Xs! DLPC IPS! Whatʼs the baseline? Implicit but there!!
ER design to separate different phases of a cognitive process! Rowe et al., 2000, Science Dissociating Response Selection from Maintenance!
In Green: Maintenance Prefrontal 8 and Intra-parietal Cortex but not Prefrontal 46 In Red: Response Selection Prefrontal 46 Intra-parietal Cortex
Area 8 Dynamics of Activation in Maintenance Areas IntraParietal
Dynamics of Response Selection Related Activation Area 46 Intraparietal Cortex
Rapid event-related fmri with randomized stimulus presentation.!! Stimulus event = impulse -> convolve with HDR!! Derive overall response!
HDR: Timing of fmri Signal! - Use an hypothesized HDR (Gamma) - Use a first set of data to estimate HDR (similar across the brain but varies across Ss), and then use this HDR as model - Use the data to estimate the HDR From Vanzetta and Grinvald, Science, 286, 1999
Rapid event-related fmri with randomized stimulus presentation.!! Used the data to estimate HDR!! Checkerboard, 1s duration, LVF or RVF!! Randomized presentation order (THIS IS KEY)!! Varying ISI!
Areas of BOLD activity can be detected using very short ISI as long as order of stimulus is random!! Caveat: each condition activates very strongly and selectively only one of the brain area of interest!
Effects of inter-stimulus interval upon event-related fmri activity!! Finger tapping task lead by a flashing stimulus!! Stimulus Duration (SD) and ISI systematically varied! Can resolve stimulus alternation with long ISI but not at short ISI.!
! Same effect in motor cortex!
Key to event-related design!! Randomize the conditions! Use variable length ISI! Ensures:!!Fair baseline!!minimize length of experiment!!bold signal does not saturate with repeated presentations effectively becoming equivalent to a blocked design!
Pluses and Minuses of Event Related Design!! Good estimation of HDR (relative timing of activation; separate different phases of a task)!! Randomization of condition (P300)!! Transient activation rather than steady state!! Trial sorting based on coding known after the fact (behavior - memory experiment)!
Trial Sorting: Memory!! Record activation during study period - See list of words - Judge whether it is edible or not:! Phone! Tomato! Bread! Table! Candle!..!! 1/2 hour later; old/new recognition task!! Analyze activation based on correct or incorrectly remembered!
Event fmri has sufficient power for single events!! BOLD signal variations recovered for each event, independently of the other event!
From OʼConnor and Kanwisher, JCN, 2001!
Pluses and Minuses of Event Related Design!! Good estimation of HDR (relative timing of activation; separate different phases of a task)!! Randomization of condition (P300)!! Transient activation rather than steady state!! Trial sorting based on coding known after the fact (behavior - memory experiment)! MINUSES!! Low Power compared to block for equal imaging time (but still pretty good)!! Longer scanning time than blocked design!
Semirandom designs that combine features of blocked and event-related designs.!! Rather than being truly blocked, the presentation of the event is probabilistic within blocks (75% in block 1; 25% in block 2)!! Advantage:!! provide robust signal -> good for detection.!! Can be used to estimate HDR -> ok for estimation!
Semi-random designs that combine features of blocked and event-related designs.!! Assumes that cognitive process engaged by each event is unrelated to its surroundings; in other words blocking does not induce a cognitive strategy above and beyond that studied by manipulating the independent variable (unlikely for any cognitive experiment!) - ex. Lexical Decision!
Mixed fmri design.!! Example:!! Blocks: Recognition Task (have you seen that word before during study?) vs NonTask, fixation blocks!! Item: Word studied before, new words, or just fixation!! Analysis:! Recognition Task vs Non Task -> ROIs associated with memory in general! Items that are successfully recognized vs failure of recognition -> Successful vs unsuccessful retrieval!
Transient -event related - successful vs. failed recognition! Sustained - blocked - General memory areas!
Mixed fmri design.!! Embed event-related within a block design!! Strength!! State-related process (attention, memory retrieval)! Item-related process (correct performance, successful recall/recognition etc)!