1. Fundamentals of Neuroscience Neuroimaging in Cognitive Neuroscience
James Danckert
PAS 4040

2. Functional Neuroimaging
Electrical activity
Event-related potentials (ERP), visual evoked potentials (VEP) all derivative from EEG
Stimulation
Trans-cranial magnetic stimulation – single vs. rapid pulse TMS
Metabolism
Positron Emission Tomography (PET) and Blood Oxygenated Level Dependent (BOLD) functional MRI (fMRI)

3. EEG
Large populations of neurons firing produce electrical potentials that can be measured at the scalp
Signals are passively conducted through the skull and scalp and can be amplified and measured
Difference between reference (ground) and recording electrodes are measured to give the electrical potential – electroencephalogram (EEG)

4. ERPs and VEPs EEG tends to record global brain activity
ERPs (and VEPs) are a special case of EEG
average EEG trace from a large number of trials
align signal to onset of a stimulus or response – hence event-related potential (ERP)

5. Pros and cons of ERPs. Good temporal resolution
Linked to specific physiological markers (e.g., N1, P3 etc. which in turn can be linked to known cognitive processes)
Cons
Poor spatial resolution
Difficult to get at some brain regions (OFC, temporal cortex)

6. Transcranial Magnetic Stimulation (TMS)
Thompson (1910) placed head between two coils and stimulated at ~ 42 Hz
saw flashing lights – magnetophosphenes
was probably stimulating the retina and not the visual cortex
Cowey and Walsh, 2001

7. TMS
TMS applies a magnetic pulse to a certain brain region to temporarily modulate the function of that region

8. TMS
circular coil
induced current
the induced current in the tissue is in the opposite direction to that of the coil
the intensity of the signal drops off towards the centre and outside of the coil
Cowey and Walsh, 2001

9. TMS
little or
no change
maximum
hyperpolarization
maximum
depolarization
the flow of the current must cross the axon to cause stimulation or interruption of function (N3 will not be stimulated)
Cowey and Walsh, 2001

10. TMS

11. Spatial extent of TMS spatial extent of induced electric field
drops ~ 75% within 10 mm
affects 600 mm2 of neural tissue

12. Rapid vs. Single Pulse TMS
for single pulse TMS duration of stimulation = 1 msec, but affects motor cortex for up to 100 msec
for rapid or repetitive pulse TMS stimuli are delivered in trains with frequencies from 1 to 25 Hz (1 – 25 times per second)
duration of after-effects for rapid pulse TMS anywhere from msec to several seconds

13. Transcranial magnetic stimulation (TMS / rTMS)
excitatory or inhibitory reversible effects depending on site and parameters of stimulation (e.g. frequency of pulses)
-> facilitates or slows down cognitive process/behavior
when inhibitory, referred to as ‘virtual lesion technique’
can give precise timing information (msec level) due to transient nature of effects
rTMS is beginning to be used as a treatment for depression (focus is on DLPFC)

14. TMS Poor spatial localisation – how focal is the stimulation?
Can’t stimulate certain areas (e.g., temporal lobe) and can only stimulate cortical surface
Good temporal resolution
Can presumably disrupt individual processes within a task.
Distance effects – changed interactions due to stimulation
Can induce seizures (particularly rTMS)

15. Frameless stereotaxy and fMRI
areas can be identified functionally and then used to position the coil in a TMS study using the frameless stereotaxy method
Paus is attempting to directly combine fMRI and TMS – with TMS pulses delivered in between fMRI runs

16. Metabolic Imaging
Two main techniques – positron emission tomography (PET) and functional MRI (fMRI)
Activity in cells requires energy (oxygen and glucose)
Increased neural activity will lead to changes in cerebral blood volume (CBV), cerebral blood flow (CBF) and the rate of metabolism of glucose and oxygen (CRMGl and CRMO)
These changes in blood flow and metabolism can be measured using PET and fMRI

17. Positron Emission Tomography (PET)
Measures local changes in cerebral blood flow (CBF) or volume and can also be used to trace certain neurotransmitters (but can only do one of these at a time)
Radioactive isotopes are used as tracers
The isotopes rapidly decay emitting positrons
When the positrons collide with electrons two photons (or gamma rays) are emitted
The two photons travel in opposite directions allowing the location of the collision to be determined

18. Positron Emission Tomography (PET)

19. PET and subtraction
Run two conditions – stimulation (e.g., look at visual images) vs. control (e.g., look at blank screen)
Measure the difference in activation between the two images (i.e., subtract control from stimulation)
This provides a picture of regional cerebral blood flow relative to visual stimulation.

20. Motion vs. colour.
Subject views coloured screen (left) vs. moving random black and white dots (right)
Both task activate early visual areas (V1 and V2)
Subtracting the two images reveals different brain areas for colour (V4) vs. motion (V5) processing

21. PET vs. fMRI
PET allows you to track multiple metabolic processes so long as the emitted photon can be detected – allows imaging of some neurotransmitters
PET is invasive – radioactive isotopes can only be administered (at experimental levels) every 4 – 5 years
fMRI has much greater spatial resolution (~ mms)
fMRI has greater temporal resolution – can detect activation to stimuli appearing for less than a second (PET is limited by the half life of the isotope used)

22. fMRI

23. Magnet safety
very strong magnetic fields – even large and heavy objects can ‘fly’ into the magnet bore

24. Cerebral blood supply. Arterioles Capillaries Y=95% at rest.
Y=100% during activation.
25 mm diameter.
<15% blood volume of cortical tissue.
Venules
Y=60% at rest.
Y=90% during activation.
25-50 mm diameter.
40% blood volume of cortical tissue.
Red blood cell
6 mm wide and 1-2 mm thick.
Delivers O2 in form of oxyhemoglobin.
Capillaries
Y=80% at rest.
Y=90% during activation.
8 mm diameter.
40% blood volume of cortical tissue.
Primary site of O2 exchange with tissue.
Transit Time = 2-3 s

25. Cerebral blood supply.

26. fMRI Deoxyhaemoglobin is paramagnetic
When neural activity increases more oxygenated blood than is needed is delivered to the site
This leads to an imbalance in oxyhaemoglobin and deoxyhaemoglobin – more oxy than deoxy
fMRI is able to measure this difference due to the different magnetic properties of oxy and deoxyhaemoglobin

27. fMRI and BOLD
blood oxygenated level dependent (BOLD) signal is actually a complex combination of:
rate of glucose and oxygen metabolism
CBV
CBF
same subtraction logic used in PET is used in fMRI

28. fMRI – block design
fMRI (like PET) began examining brain activity using block designs
colours
rest
motion

29. fMRI – event-related design
allows randomization of stimuli (not possible in PET)

30. fMRI – event-related design
BOLD response has a predictable form
In rapid event-related designs the signal to a given trial type is deconvolved using models of the BOLD response

31. Linearity of BOLD response
Dale & Buckner, 1997
Linearity:
“Do things really add up?”
red = 2 - 1
green = 3 - 2
Sync each trial response to start of trial
Not quite linear but good enough !

32. Fixed vs. Random Intervals
If trials are jittered,  ITI  power
Source: Burock et al., 1998

33. fMRI spatial resolution
images can be co-registered to the subject’s own brain (not an average brain as in PET)
PET
fMRI

34. red = wrist; orange = shoulder
fMRI and topologies
Using fMRI to “map” different brain functions
Penfield’s maps
Servos et al., 1998
red = wrist; orange = shoulder

35. Retintopy 8 Hz flicker (checks reverse contrast 8X/sec)
EXPANDING RINGS
ROTATING WEDGES
8 Hz flicker (checks reverse contrast 8X/sec)
good stimulus for driving visual areas
subjects must maintain fixation (on red dot)
Source: Jody Culham

36. EXPECTED RESPONSE PROFILE OF AREA RESPONDING TO STIMULUS
To analyze retinotopic data:
Analyze the data with a set of functions with the same profile but different phase offsets.
For any voxels that show a significant response to any of the functions, color code the activation by the phase offset that yielded maximum activation (e.g., maximum response to foveal stimulus = red, maximum response to peripheral stimulus = pink)
time = 0
time = 20 sec
time = 40 sec 20 40 60
STIMULUS
time = 60 sec
TIME 
Source: Jody Culham

37. Retintopy: Eccentricity
calcarine
sulcus
left occipital
lobe
right occipital
lobe
foveal area represented at occipital pole
peripheral regions represented more anteriorly

38. Retinotopy
Source: Sereno et al., 1995

39. Other Sensory “-topies”
Audition:
Tonotopy
cochlea
Sylvian fissure
temporal lobe

40. Marty Sereno’s web page
Saccadotopy
delayed saccades
move saccadic target systematically around the clock
Source: Sereno et al., 2001
Marty Sereno’s web page

41. Break

42. Finding the human homologue of monkey area X!
recent research has used monkey neurophys to guide fMRI in humans
Dukelow et al. 2001

43. Problems with the search for homologues
Absence of activation doesn’t mean the absence of function
Presence of activation doesn’t imply sole locus of function
But our brains are different!
Confirmatory hypotheses
Dukelow et al. 2001

44. fMRI and diagnosis
fMRI is starting to be used in patients with epilepsy
one goal is to use this as a tool to localise language, memory etc. prior to surgery
another goal would be to use fMRI to study the propogation of seizures
in stroke patients fMRI can be used to chart recovery of function

45. Patient SP – congenital porencephalic cyst
Left
Right

46. SP - motor strip
motor strip
sequential tapping
alternating tapping

47. SP – somatosensory strip
sequential tapping
alternating tapping

48. superior parietal sequential tapping alternating tapping e g n a h c l
6.0 6 4 2 -1 1 3 5 % s i g n a l c h e
images g n a
4.0 h c l
2.0 a n g
0.0 s i %
-2.0 1 21 41
images

49. Broca’s area? name animals name objects non-word sounds (‘ba’) e h c l% s i g n a l c h e
images 1 21 41 2 -1

50. left occipital name animals name objects non-word sounds (‘ba’) e h c% s i g n a l c h e
images 1 21 41 2 -1

51. fMRI and cognition What not to do – poorly designed tasks!
What is the right inferior parietal lobe’s contribution to movement control?
spatial component of movements
compare imagined movements with only a spatial component vs. movements with a sequential component

52. spatial only
complex sequence

53. Bilateral FEF

54. Supplementary Motor Area (SMA)

55. Bilateral superior parietal

56. Inferior parietal cortex
Left
Right
Anterior
Posterior L R
complex sequence only
alternation only
both

57. Design Problems Boy, you must be rich then!!!
What could the right vs. left parietal difference be due to?
Attention? – possibly!
Differences in eye movements? – maybe!
Were the tasks really different in the intended way?
Perhaps – both tasks were spatial in nature and both tasks had a sequential component, so…
So did you just test task difficulty?
Maybe, what of it?
Why is right parietal more active for less difficult tasks then?
I don’t know and I don’t care, piss off! I’m gonna start again!
Boy, you must be rich then!!!

58. Confirming modularity
Nancy Kanwisher and the parahippocampal recliner region!

59. Is that all there is to it?
Alex Martin and co. suggest that the FFA responds to other kinds of objects too
Isabelle Gauthier and co. suggest that it is expertise with faces which drives the activation

60. Exploring behaviours Prism adaptation ameliorates neglect – how?
First, explore the direct effects of prism adaptation in the healthy brain.
Clower et al 1996 used PET to do this but reversed the direction of prismatic shift every 5 trials.

61. Prism Adaptation – Rossetti and colleagues
prisms shift world further to the right (into the patient’s ‘good’ field)
patient’s movements compensate for the prismatic shift – in the opposite direction
after effects lead to better processing of previously neglected stimuli

62. Setup.

63. Protocol I. 2 sec 2 sec 0.5 sec 11.5 sec 2 sec
5 runs with prisms (50 trials)
5 runs without prisms (50)
2 sec

64. Protocol II.
2 sec volumes – so 2 sec for critical stimulus (the target) and 12 sec
for post stimulus return to baseline (a la Bandettini).

65. Protocol III. 4T scanner at Robarts 17 pseudo-axial slices 5 mm thick
TR 2 sec
2-shot EPI sequence
Co-registered to 128 slice
anatomical

66. Adapting in the magnet.
mean shift = mm

67. Finding ROIs.
med frontal (SMA)
right sup par
left sup par

68. Modeling the peak activation across trials.
Linear
Logarithmic

69. Left and right superior parietal cortices.
Left Superior Parietal
-0.5
0.5 1
1.5 2
2.5 3 4 5 6 7 8 9 10
trial
max % signal change
r2=0.13
Right Superior Parietal
-0.5
0.5 1
1.5 2
2.5 3 4 5 6 7 8 9 10
trial
max % signal change
r2=0.15

70. Cerebellar ROIs. Medial Cerebellum r2=0.14 Right Lateral Cerebellum
-0.5
0.5 1
1.5 2
2.5 3 4 5 6 7 8 9 10
trial
max % signal change
r2=0.14
Right Lateral Cerebellum
-0.5
0.5 1
1.5 2
2.5 3 4 5 6 7 8 9 10
trial
max % signal change
r2=0.42

71. SMA. transverse sagittal r2 = 0.37 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 1.2
trial
max % signal change
(group mean) 2 3 4 5 6 7 8 9 10
r2 = 0.37

72. Bottom line?
Difficult to image the direct effects of adaptation in normals.
Image “good adaptors” OR change protocol to look at after effects of adaptation – with all its problems…

73. I wonder if fMRI could be used to cure cancer?
Conclusions?
fMRI should be used for good and not evil!
I wonder if fMRI could be used to cure cancer?

74. Acknowledgements fMRI of epilepsy patient fMRI of prism adaptation
Stacey Danckert
Seyed Mirsitari
David Carey
Mel Goodale
Ravi Menon
Jody Culham
fMRI of prism adaptation
Susanne Ferber
Stacey Danckert
Mel Goodale
Yves Rossetti
fMRI of imagined movements
it was all my fault!

75. End of Lecture