Top Banner
89

Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Dec 17, 2015

Download

Documents

Aldous Lang
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Page 1: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.
Page 2: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Shulman and Rothman PNAS, 1998

In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) methods, which localize brain activities. These functional imaging methodologies map neurophysiological responses to cognitive, emotional, or sensory stimulations. The rapid experimental progress made by using these methods has encouraged widespread optimism about our ability to understand the activities of the mind on a biological basis. However, the relationship between the signal and neurobiological processes related to function is poorly understood, because the functional imaging signal is not a direct measure of neuronal processes related to information transfer, such as action potentials and neurotransmitter release. Rather, the intensity of the imaging signal is related to neurophysiological parameters of energy consumption and blood flow. To relate the imaging signal to specific neuronal processes, two relationships must be established…

The first relationship is between the intensity of the imaging signal and the rate of neurophysiological energy processes, such as the cerebral metabolic rates of glucose (CMRglc) and of oxygen (CMRO2).  The second and previously unavailable relationship is between the neurophysiological processes and the activity of neuronal processes. It is necessary to understand these relationships to directly relate functional imaging studies to neurobiological research that seeks the relationship between the regional activity of specific neuronal processes and mental processes.

Page 3: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Shulman and Rothman PNAS, 1998

Psychology

CMRglc

NeuronalNeuroenergetics

MentalImage Signal

NeuroscienceCMRO2

CBF

Page 4: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Let’s back up…What do we know for sure about

fMRI?

Page 5: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

280 million Hb molecules per red blood cell

Hemoglobin Molecule

Page 6: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

L. Pauling and C. Coryell The Magnetic Properties and Structure of Hemoglobin, Oxyhemoglobin and Carbonmonoxy hemoglobin, PNAS, vol. 22, pp. 210-216, 1936.

Different magnetic properties of hemoglobin and deoxyhemoglobin

Page 7: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Hemoglobin Molecule

Page 8: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.
Page 9: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Baseline

Task

from Mosley & Glover, 1995

Blood Oxygenation Level Dependent Imaging

Page 10: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Brain or Vein?

Page 11: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.
Page 12: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Large Vessel Contributions to BOLD Contrast

Virchow-Robin Space

Page 13: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Intravascular

Perivascular

Extravascular

Page 14: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

3

z = 1.64 Small

Large

Courtesy of Dr. Allen Song, Duke University

Isotropic Diffusion Weighted Spiral Imaging at 4T

Page 15: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

9 sec

9 sec

a

b

Page 16: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Diffusion-weighted (b factor = 54)

Diffusion-weighted (b factor = 108)

Subject 41057, Slice 12, 4.0 Tesla

ADC masked by BOLD activation

BOLD activation (b factor = 0)

Page 17: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Diffusion-weighted (b factor = 54)

Diffusion-weighted (b factor = 108)

Subject 41037, Slice 183, 4.0 Tesla

ADC masked by BOLD activation

BOLD activation (b factor = 0)

Page 18: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Diffusion-weighted (b factor = 54)

Diffusion-weighted (b factor = 108)

Subject 41037, Slice 177, 4.0 Tesla

ADC masked by BOLD activation

BOLD activation (b factor = 0)

Page 19: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

BOLD activation (b factor = 0) ADC masked by BOLD activation

Subject 41037, Slice 177, 4.0 Tesla

Page 20: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Negative dips

Page 21: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Vanzetta and Grinvald, Science, 286: 1555-1558, 1999

Phosphorescence Decay Time(Oxyphor R2 oxygen tension-sensitive phosphorescent probe)

Page 22: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Vanzetta and Grinvald, Science, 286: 1555-1558, 1999

Phosphorescence Decay Time(Oxyphor R2 oxygen tension-sensitive phosphorescent probe)

Page 23: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Vanzetta and Grinvald, Science, 286: 1555-1558, 1999

Oxy Hbdeoxy Hb

Page 24: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Berwick et al, JCBFM, 2002

Optical imaging of rat barrel cortexHb02= oxyhemoglobin, Hbr = deoxyhemoglobin, Hbt = total blood flow

Page 25: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

N. Logothetis, Nature Neuroscience, 1999

Functional Imaging of the Monkey Brain

Page 26: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Hu, Le, Ugurbil MRM, 1997

Early Response in fMRI

Page 27: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Hu, Le, Ugurbil MRM, 1997

Early Response in fMRI

Page 28: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

What triggers blood flow?

Page 29: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Arterioles (10 - 300 microns)precapillary sphincters

Capillaries (5-10 microns)Venules (8-50 microns)

Page 30: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Tissue factors

• K+

• H+

• Adenosine

• Nitric oxide

Page 31: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

C. Iadecola, Nature Neuroscience, 1998Commentary upon Krimer, Muly, Williams and Goldman-Rakic, Nature Neuroscience, 1998

Neuronal Control of the Microcirculation

Page 32: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998

Pial Arteries

10 m

Noradrenergic Dopamine

Page 33: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998

Dopamanergic terminals associated with small cortical blood vessels

10 m

Page 34: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998

Dopamanergic terminals associated with small cortical blood vessels

2 m

2 m

400 nm

400 nm

Page 35: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Krimer, Muly, Williams, Goldman-Rakic, Nature Neuroscience, 1998

Perivascular iontophoretic application of dopamine

18-40 s 40-60 s

Page 36: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Let’s back up again…Why isn’t all the oxyHb used up?

Page 37: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Uncoupling…

Page 38: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

glucose

pyruvate

Glucose 6 phosphate

Fructose – 1,6-phosphate

TCAcycle

lactate

Net +2 ATP

Net +36 ATP

glucose

O2

CO2 + H20

Page 39: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Shulman and Rothman PNAS, 1998

Stimulation Change CMRglc Change CMRO2 SourceVisual 51 5 Fox et al. 1988

28 28 Marrett et al. 199329 29 Marrett et al. 1993

16 Davis et al. 199823 Chen et al. 199324 Reivich et al. 1984

Mean 31 20

Cognitive 12 Roland et al. 1987Seizure 400 267 Borgstrom et al. 1976

Page 40: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Shulman and Rothman PNAS, 1998

Proposed pathway of glutamate / glutamine neurotransmitter cycling between neurons and glia, whose flux has been quantitated recently by 13C MRS experiments. Action potentials reaching the presynaptic neuron cause release of vesicular glutamate into the synaptic cleft, where it is recognized by glutamate receptors post-synaptically and is cleared by Na+ -coupled transport into glia. There it is converted enzymatically to glutamine, which passively diffuses back to the neuron and, after reconversion to glutamate, is repackaged into vesicles. The rate of the glutamate-to-glutamine step in this cycle (Vcycle), has been derived from recent 13C experiments.

Page 41: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Sibson et al. PNAS, 1998

Stimulation Change CMRglc Change CMRO2 SourceVisual 51 5 Fox et al. 1988

28 28 Marrett et al. 199329 29 Marrett et al. 1993

16 Davis et al. 199823 Chen et al. 199324 Reivich et al. 1984

Mean 31 20

Cognitive 12 Roland et al. 1987Seizure 400 267 Borgstrom et al. 1976

Page 42: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Heeger, Nature Neuroscience 2002

Page 43: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Ito et al. JCBFM, 2001

Stimulation Change CMRglc Change CMRO2 SourceVisual 51 5 Fox et al. 1988

28 28 Marrett et al. 199329 29 Marrett et al. 1993

16 Davis et al. 199823 Chen et al. 199324 Reivich et al. 1984

Mean 31 20

Cognitive 12 Roland et al. 1987Seizure 400 267 Borgstrom et al. 1976

Page 44: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Relationship of BOLD to neuronal activity

Page 45: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Attwell and Laughlin, JCBFM, 2001

Brain Energetics

Page 46: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Attwell and Laughlin, JCBFM, 2001

Brain Energetics

Page 47: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Rees et al. Nature Neuroscience 2000

Page 48: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Heeger, Nature Neuroscience 2000

Page 49: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Lauritzen, JCBFM, 2001

Page 50: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Lauritzen, JCBFM, 2001

Climbing Fiber Stimulation

Page 51: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Lauritzen, JCBFM, 2001

Climbing Fiber Stimulation

Page 52: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Lauritzen, JCBFM, 2001

Parallel Fiber Stimulation

Page 53: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Lauritzen, JCBFM, 2001

Harmaline IP synchronizes inferior olive

Page 54: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Smith et al. PNAS, 2002

Page 55: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Hyder et al. PNAS, 2002

Stimulation Change CMRglc Change CMRO2 SourceVisual 51 5 Fox et al. 1988

28 28 Marrett et al. 199329 29 Marrett et al. 1993

16 Davis et al. 199823 Chen et al. 199324 Reivich et al. 1984

Mean 31 20

Cognitive 12 Roland et al. 1987Seizure 400 267 Borgstrom et al. 1976

Page 56: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Spatial co-localization?

Page 57: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

How neuronal activity changes cerebral blood flow is of biological and practical importance. The rodent whisker-barrel system has special merits as a model for studies of changes in local cerebral blood flow (LCBF).

Whisker-activated changes in flow were measured with intravascular markers at the pia. LCBF changes were always prompt and localized over the appropriate barrel. Stimulus-related changes in parenchymal flow monitored continuously with H2 electrodes recorded short latency flow changes initiated in middle cortical layers. Activation that increased flow to particular barrels often led to reduced flow to adjacent

cortex.

The matching between a capillary plexus (a vascular module) and a barrel (a functional neuronal unit) is a spatial organization of neurons and blood vessels that optimizes local interactions between the two. The paths of communication probably include: neurons to neurons, neurons to glia, neurons to vessels, glia to vessels, vessels to vessels and vessels to brain. Matching a functional grouping of neurons with a vascular module is an elegant means of reducing the risk of embarrassment for energy-expensive neuronal activity (ion pumping) while minimizing energy spent for delivery of the energy (cardiac output). For imaging studies this organization sets biological limits to spatial, temporal and magnitude resolution. Reduced flow to nearby inactive cortex enhances local differences Woolsey et al. Cerebral Cortex, 95: 7715-7720, 1996

Whisker Barrel Model

Page 58: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Yang, Hyder, Shulman PNAS, 93: 475-478, 1996

Rat Single Whisker Barrel fMRI Activation

7 Tesla200 m x 200 m x 1000 m

Page 59: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Berwick et al, JCBFM, 2002

Optical imaging of rat barrel cortexHb02= oxyhemoglobin, Hbr = deoxyhemoglobin, Hbt = total blood flow

Page 60: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Berwick et al, JCBFM, 2002

(a) Outside activated region, (b) ipsilateral whisker

Page 61: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Relationship between field potentials and functional MRI

Page 62: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

-1

0

1

2

3

4

5

6

7

-5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12

100ms

500ms

1500ms

-1

0

1

2

3

4

5

6

7

-5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12

100ms

500ms

1500ms

-1

0

1

2

3

4

5

6

7

-5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12

100ms

500ms

1500ms

1500ms

Stimulus Onset Asynchrony

(15-17 seconds)

100ms

500ms

1500ms

Stimulus Onset Asynchrony

(15-17 seconds)

100ms

500ms

Stimulus Onset Asynchrony

(15-17 seconds)

100ms

500ms

100ms

500ms

Page 63: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

LMY1

Page 64: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

- 1 5 0

- 1 0 0

- 5 0

0

5 0

1 0 0

1 5 0

2 0 0

2 5 0

- 1 0 0 0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0

1 0 0 m s5 0 0 m s1 5 0 0 m s

L P O - 3

Page 65: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

- 4 0 0

- 3 0 0

- 2 0 0

- 1 0 0

0

1 0 0

2 0 0

- 1 0 0 0 1 0 0 2 0 0 3 0 0 4 0 0 5 0 0 6 0 0 7 0 0 8 0 0 9 0 0

1 0 0 m s5 0 0 m s1 5 0 0 m s

L P O - 4

Page 66: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

-1

0

1

2

3

4

5

6

7

-5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12

100ms

500ms

1500ms

-1

0

1

2

3

4

5

6

7

-5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12

100ms

500ms

1500ms

-1

0

1

2

3

4

5

6

7

-5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 10 11 12

100ms

500ms

1500ms

1500ms

Stimulus Onset Asynchrony

(15-17 seconds)

100ms

500ms

1500ms

Stimulus Onset Asynchrony

(15-17 seconds)

100ms

500ms

Stimulus Onset Asynchrony

(15-17 seconds)

100ms

500ms

100ms

500ms

Page 67: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

LTO10

DWT1

LSOP5

LPT6

LPT7

LTO4

Page 68: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Time (msec)

SOP5

PT6

PT7

TO4

TO10

LG

FG

Pole

V1-V2

MT

Page 69: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Timing of activations compared to neuronal activation

Page 70: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Subdural Electrode Strips

Page 71: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.
Page 72: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Face-Specific N200

2 A

-500

0

500

-100 0 100 200 300 400 500 600

Faces

Flowers

Nouns

Scr Faces

Target

-500

0

500

-100 0 100 200 300 400 500 600

Faces

Flowers

Nouns

Scr Faces

Target

10

11

0 100 200 300 400 500 600

Faces

Cars

Scr Faces

Numbers

Butterflies

0 100 200 300 400 500 600

Faces

Cars

Scr Faces

Numbers

Butterflies

Faces

Cars

Scr Faces

Numbers

Butterflies

B C

LMT 11

LMT 12

LMT 10

LMT 9 RMT 1

RMT 4

RMT 3

RMT 2

2 A

-500

0

500

-100 0 100 200 300 400 500 600

Faces

Flowers

Nouns

Scr Faces

Target

-500

0

500

-100 0 100 200 300 400 500 600

Faces

Flowers

Nouns

Scr Faces

Target

10

11

10

11

0 100 200 300 400 500 600

Faces

Cars

Scr Faces

Numbers

Butterflies

0 100 200 300 400 500 600

Faces

Cars

Scr Faces

Numbers

Butterflies

Faces

Cars

Scr Faces

Numbers

Butterflies

B C

LMT 11

LMT 12

LMT 10

LMT 9 RMT 1

RMT 4

RMT 3

RMT 2

Page 73: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

RPTO 8

-300

-250

-200

-150

-100

-50

0

50

100

150

-100 0 100 200 300 400 500 600 700 800 900

Time (msec)

Fruits Face-Cap Tools Scr Faces Circles (Targets)

Page 74: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Face-House Attention Task

Page 75: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

-300

-100

100

300

-100 100 300 500 700 900 1100 1300 1500 1700 1900

Attend House

Attend Face

NBH1

CDOB1

Page 76: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Negative activations

Page 77: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Harel et al. JCBFM, 2002

Page 78: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Harel et al. JCBFM, 2002

Page 79: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Harel et al. JCBFM, 2002

Page 80: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

9 sec

9 sec

a

b

Page 81: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

180° phase-reversed responses to faces among objects

Page 82: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

41088

-8

-4

0

4

8

12

0 18 36 54 72 90 108 126 144 162 180 198 216 234 252 270 288 306

Positive ActivationNegative Activation

41088

Page 83: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Is there evidence for inhibition?

Page 84: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

-300

-200

-100

0

100

200

300

-100 0 100 200 300 400 500 600 700 800 900

LTTP2-2Letterstring -Specific

RTTP2-5Face -Specific

P200

N200

JRNFaceNoun

RTP2-5 LTTP2-2

Page 85: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

-150

-100

-50

0

50

100

0 100 200 300 400 500

FacesNouns

LOTM 8Letterstring - Specific

P200

N200

JGD

-150

-100

-50

0

50

100

150

0 100 200 300 400 500

FacesNouns

LTOI 10Letterstring - Specific

P200

N200

JWR

-100

-80

-60

-40

-20

0

20

40

60

80

100

0 100 200 300 400 500 600 700 800

FacesNouns

LTTP 2Face - Specific

P200

N200

SGN

-250

-200

-150

-100

-50

0

50

100

150

0 100 200 300 400 500 600 700 800

FacesNouns

RTTP 2Face - Specific

P200

N200

LSH

-150

-100

-50

0

50

100

0 100 200 300 400 500

FacesNouns

LOTM 8Letterstring - Specific

P200

N200

JGD

-150

-100

-50

0

50

100

150

0 100 200 300 400 500

FacesNouns

LTOI 10Letterstring - Specific

P200

N200

JWR

-100

-80

-60

-40

-20

0

20

40

60

80

100

0 100 200 300 400 500 600 700 800

FacesNouns

LTTP 2Face - Specific

P200

N200

SGN

-250

-200

-150

-100

-50

0

50

100

150

0 100 200 300 400 500 600 700 800

FacesNouns

RTTP 2Face - Specific

P200

N200

LSH

Page 86: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

-

+

Excitatory

Inhibitory

+

-

Face-specific cell Word-specific cell

N200 P200

Page 87: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.
Page 88: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Rat Olfactory Bulb Structural MRI

Yang, Renken, Hyder, Siddeek, Greer, Shepherd, Shulman PNAS, 95: 7715-7720, 1998

7 Tesla100 m x 100 m x 1000 m

Page 89: Shulman and Rothman PNAS, 1998 In this period of intense research in the neurosciences, nothing is more promising than functional magnetic resonance imaging.

Yang, Renken, Hyder, Siddeek, Greer, Shepherd, Shulman PNAS, 95: 7715-7720, 1998

Rat Olfactory Bulb fMRI Activation

7 Tesla200 m x 200 m x 1000 m