# Presentation: 652254

## Peter A. Bandettini, Ph.D

Unit on Functional Imaging Methods
&
3T Neuroimaging Core Facility

Laboratory of Brain and Cognition
National Institute of Mental Health

- Unit on Functional Imaging Methods
- &
- 3T Neuroimaging Core Facility
- Laboratory of Brain and Cognition
- National Institute of Mental Health

**Squeezing Neuronal Information **
**from Hemodynamics**

## ?

**?**

**?**

**?**

## Latency 

**Magnitude **

**Systems Level **
**Neuronal Information Extraction**

## Slide 4

## Pulse Sequence

- Sensitivity

- Spatial
- Heterogeneity

**0     1      2    3  4**

## Slide 6

## Latency

**Latency**

**Magnitude**

**+ 2 sec**

**- 2 sec**

## Venograms (3T)

**Venograms (3T)**

## Slide 9

## 0

- 5

- 10

- 15

- 20

- 25

- 30

- 100

- 200

- 300

- 400

- 500

- Number of runs

- 8 sec on/off

- 16 sec on/off

- Smallest latency
- Variation Detectable
- (ms) (p < 0.001)

- t

- 1 run:

- -1000

- -500

- 500

- 1000

- Number

- delay estimate (ms)

- delay = 107ms

**11**

- 1% Noise
- 4% BOLD
- 256 time pts /run
- 1 second TR

## Slide 11

## Hemi-Field Experiment

**Right Hemisphere**

**Left Hemisphere**

## Hemi-field with 500 msec asynchrony

- <date/time>

**Percent**

**MR**

**Signal**

**Strength**

**Time (seconds)**

**Average of 6 runs     Standard Deviations Shown**

## =

**+ 2.5 s**

**- 2.5 s**

**0 s**

**500 ms**

**500 ms**

**Right**** ****Hemifield**

**Left Hemifield**

**-**

## Hemodynamic Response Modulation

**Bottleneck**
**In Processing**
**(upstream)**

**Delayed**
**Processing**
**(downstream)**

**Hemodynamic Response Modulation**

## Use of Task Timing Modulation to Extract Processing Streams  

- Use of Task Timing Modulation to Extract Processing Streams

- Stimuli – Six-letter English words and pronounceable non-words.
- 	   Each word or non-word was rotated either 0, 60,or 120 degrees
- Task – Lexical Decision (word / non-word).
- Dependent Measures – Percent Correct and Reaction Time.

- Hypotheses :
- 	**1) Stimulus rotation of 120 degrees will result in:**
- 		a) Longer Reaction Times
- 		b) Stimulus rotation demands a change in perceptual
- 		perspective prior to linguistic processing. This will
- 		result in a delayed IRF onset in areas involved in
- 		Lexical and Pre-Lexical processing.
- 	 2**) Lexical discrimination will result in :**
- 		a) Longer Reaction Times for non-words due to
- 		increased Pre-Lexical processing demands.
- 		b) Wider IRF in Inferior Frontal cortex for non-words
- 		c) Delayed IRF onset in Left Middle Frontal Cortex

## Lexical Delay

- smudge

- slouch

- dierts

- cuhlos

- gedmus

**Lexical Delay**

- Words

- Non-Words

**Rotational Delay**

- 00

- 600

- 1200

- Mean
- Reaction Time

- 823 ms

- 891 ms

- 1446 ms

- 986 ms

- 1219 ms

- Mean
- Reaction Time

## Slide 18

## Graphs depicting the estimated Impulse Response Functions.

**Inferior Frontal Gyrus**

**Middle Temporal Gyrus**

**Pre-Central Gyrus**

**Magnitude**

**Delay**

**Width**

- Warm colors are areas where Words > Non-words.  Cool colors (blues) are areas
- Where Non-words > words. The Left hemisphere is toward the left margin.
- The green arrows highlight the inferior frontal gyrus.

## 11026–11031  PNAS  September 26, 2000 vol. 97  no. 20

## Laminar Specificity of fMRI Onset Times During Somatosensory Stimulation in Rat

**Afonso C. Silva and Alan P. Koretsky**
***Laboratory of Functional and Molecular Imaging***
**National Institute of Neurological Disorders and Stroke**
**Bethesda, Maryland, USA**

## Can fMRI be used to distinguish neuronal signaling within laminar sub-regions of the brain?

## fMRI Methods

- 11.7T/31cm magnet (Magnex Scientific, Ltd.)
- AVANCE electronics (Bruker-Biospin, Inc.)
- Conventional gradient-echo images
- FOV = 1.28 x 1.28 x 0.2 cm3
- TE = 10 ms, TR = 40 ms, tip-angle ≈ 11°
- Matrix size:
- 64 x 64 (200 x 200 x 2000 m3), 2.5 s/frame
- 128 x 128 (100 x 100 x 2000 m3, 5.0 s/frame
- 256 x 256 (50 x 50 x 2000 m3), 10 s/frame
- CBV: 20 mg/kg of AMI-227 (Advanced Magnetics, MA)

## Somatosensory Stimulation 

- Electrical stimulation of the forepaw:
- Two needle electrodes inserted subcutaneously
- Stimulation parameters: 2.0 mA; 3 Hz; 0.3 ms
- Paradigm:
- Single stimulation **off – on – off** epoch
- 	               24        12      24   images
- 	               60        30      60   seconds,   200 x 200 m2
-                    240      120    240   seconds,     50 x   50 m2
-   Multiple stimuli block design
- 	                     325     100    325   images     200 x 200 m2
- 		               13         4      13   seconds,   repeated 64 times

## MRI of Functional Hemodynamics

- Gradient-Echo Sequence
- Resolution = 100x100x2000 m3

- Iron Oxide Contrast Agent
- Resolution = 100x100x2000 m3

- BOLD

- rCBV

## Mapping Onset Times of fMRI Response

- Hemodynamic response is stable if duty-cycle of repeated stimuli is low enough
_*Strategy*_: to acquire multiple high-resolution images using conventional GRE-MRI, swapping phase-encode loop with image repetition loop to obtain one k-space line for all images per stimulus epoch
- Spatial in-plane resolution: 200 x 200 m2
- Temporal resolution: 40 ms

## Averaged BOLD Time-Courses

## Onset Time Detail

## Latency 

**Magnitude **

**Systems Level **
**Neuronal Information Extraction**

## Different stimulus “ON” periods

- measured

- linear

- Signal

- 0.25 s

- 0.5 s

- 1 s

- 2 s

- 20 s

- Stimulus
- timing

- BOLD
- Response

*Brief stimuli produce larger responses than expected*

**Dynamic Nonlinearity Assessment**

**R. M. Birn, Z. Saad, P. A. Bandettini, (2001) “Spatial heterogeneity of the nonlinear dynamics in the fMRI BOLD response.” *****NeuroImage*****, 14: 817-826.**

## Spatial variation of linearity

*R.M. Birn, et al. Neuroimage 14, 817-26, 2001*

- Visual

- Motor

**Notes:**
(NL) does indeed vary over space, but not correlated with either latency or magnitude of response (often used to char. vessels).  What is interesting is that the differences appear in different functional areas, such as...  This suggests that perhaps the neurons aren’t doing what we think – i.e. that the neuronal response is not simply a boxcar.

## Results – visual task

- Nonlinearity

- Magnitude

- Latency

**R. M. Birn, Z. Saad, P. A. Bandettini, (2001) “Spatial heterogeneity of the nonlinear dynamics in the fMRI BOLD response.” *****NeuroImage*****, 14: 817-826.**

## Results – motor task

- Nonlinearity

- Magnitude

- Latency

## Sources of this Nonlinearity

- Neuronal
- Hemodynamic
- Oxygen extraction
- Blood volume dynamics

- Volume

- Flow In

- Flow Out

- Oxygen Extraction

## BOLD Correlation with Neuronal Activity

**Logothetis et al. (2001) “****Neurophysiological investigation of the basis of the fMRI signal” ****Nature, 412, 150-157.**

**P. A. Bandettini and L. G. Ungerleider, (2001) “From neuron to BOLD: new connections.” Nature Neuroscience, 4:  864-866.**

## Results – constant gratings

- Results – constant gratings

- 0

- 1000

- 2000

- 3000

- 0

- 1

- 2

- 3

- Measured Amplitudes

- Stimulus Duration (ms)

- Amplitude (%)

- Estimated
- Neuronal
- activity

**a** = initial slope

**b** = final slope

- 200

*Simulation*

**Notes:**
Averaged over ROI (entire activated region) and across 5 subjects.  (Each subject showed a similar response, but noisier.)

What can be seen: 

## Slide 38

## Logothetis et al. (2001) “Neurophysiological investigation of the basis of the fMRI signal” Nature, 412, 150-157

**S. M. Rao et al, (1996) “Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex.” *****J. Cereb. Blood Flow and Met.***** 16, 1250-1254.**

## Ziad Saad, et al (Submitted)

- Continuously Growing
- Activation Area

- Inflection Point

- CC Histogram

**Notes:**
(perhaps show only six and keep going up till 22).
This is a plot of the number of activated voxels detected versus the number of averaged scans.
This data is from the 3T.
The red data represents positive responses and the green data represents negative responses. 
Different dots at any one number of average scans represents the estimates from the different permutations.
The curves represent linear fits to the average number of activated voxels versus Navg.
Note the dramatic increase in the number of activated voxels with Navg. This function fits a linear curve with a correlation of ~92-97%. 
Note also the very large scatter of the number of activated voxels for voxels in a single rep. (perhaps put the subject performance and the number of voxels versus repno here ...)

## Latency 

**Magnitude**

**Systems Level **
**Neuronal Information Extraction**

## FIM Unit & FMRI Core Facility 	

**Peter Bandettini**
**Staff Scientists:**
**Sean Marrett**
**Jerzy Bodurka**
**Frank Ye**
**Wen-Ming Luh**
**Computer Specialist:**
**Adam Thomas**
**Post Docs:**
**Rasmus Birn**
**Hauke Heekeren**
**David Knight**
**Patrick Bellgowan**
**Ziad Saad**

**FIM Unit & FMRI Core Facility **

**Graduate Student:**
**Natalia Petridou**
**Post-Back. IRTA Students:**
**Elisa Kapler**
**August Tuan**
**Dan Kelley**
**Visiting Fellows:**
**Sergio Casciaro**
**Marta Maieron**
**Guosheng Ding**
**Clinical Fellow:**
**James Patterson**
**Psychologist:**
**Julie Frost**

**Summer Students:**
**Hannah Chang**
**Courtney Kemps**
**Douglass Ruff**
**Carla Wettig**
**Kang-Xing Jin**** **
**Program Assistant:**
**Kay Kuhns**
**Scanning Technologists:**
**Karen Bove-Bettis**
**Paula Rowser**

## BOLD

**BOLD**

*Rest**	**	**Activation*

**P. A. Bandettini, E. C. Wong, Magnetic resonance imaging of human brain function: principles, practicalities, and possibilities, *****in*****  "Neurosurgery Clinics of North America: Functional Imaging" (M. Haglund, Ed.), p.345-371, W. B. Saunders Co., 1997. **

**Perfusion**

## Anatomy

**Anatomy**

**BOLD**

**Perfusion**

**P. A. Bandettini, E. C. Wong, Magnetic resonance imaging of human brain function: principles, practicalities, and possibilities, *****in*****  "Neurosurgery Clinics of North America: Functional Imaging" (M. Haglund, Ed.), p.345-371, W. B. Saunders Co., 1997. **

## Rotational effect maps

**Delay**

**Width**

**Rotational effect maps**

- Warm colors are areas where Non-rotated stimuli > rotated.  Cool colors (blues) are areas where Rotated stimuli > Non-rotated. The Left hemisphere is toward the left margin.

**Non-rotated**** vs. ****120****o**** rotated**

**Non-rotated**** vs. ****60****o**** rotated**