1. Brain Mapping and Functional Brain Imaging Ling 411 – 09

2. Methods of localization  Lesion studies The traditional method For a long time, the only method  Selective anesthetization  Intra-operative mapping Started by Penfield and Roberts, 1960’s  Transcranial magnetic stimulation (TMS) Recently developed Very promising  Functional brain imaging Currently very popular Many techniques

3. Methods of localization  Lesion studies The traditional method For a long time, the only method  Selective anesthetization  Intra-operative mapping Started by Penfield and Roberts, 1960’s  Transcranial magnetic stimulation (TMS) Recently developed Very promising  Functional brain imaging Currently very popular Many techniques

4. Selective anesthetization  Temporarily anesthetize a portion of cortical tissue Injection of a drug in an artery  Usually sodium amytal  Rapid onset and short duration of effects Shuts down a portion of cortex till drug wears off  Usually injected in a carotid artery Left or right Shuts down a whole hemisphere The Wada test  In 10% of cases the findings disagree with those from fMRI

5. Methods of localization  Lesion studies The traditional method For a long time, the only method  Selective anesthetization  Intra-operative mapping Started by Penfield and Roberts, 1960’s  Transcranial magnetic stimulation (TMS) Recently developed Very promising  Functional brain imaging Currently very popular Many techniques

6. Electrical stimulation mapping (A type of intra-operative mapping)  Early work by Penfield and Roberts Montreal  More recently, George Ojemann – neurosurgeon, U. of Washington Book: Conversations with Neil’s brain (with W. Calvin, 1994) Neil, a patient, suffers from epilepsy  Currently, in Texas Medical Center Nitin Tandon, UT

7. Intra-operative brain mapping  Performed on exposed neural tissue After craniotomy Used only in pathological conditions  E.g., epilepsy  Methods in use Electrical stimulation mapping Electrocorticograms Microelectrode recordings

8. George Ojemann and Neil’s Brain (electrical stimulation mapping)  George Ojemann – neurosurgeon, U. of Washington Book: Conversations with Neil’s brain (with W. Calvin, 1994) Neil, a patient, suffers from epilepsy  Intraoperative probing of part of Neil’s brain In the area suspected of causing seizures Probing to spare vital linguistic functions Additional probing for research

9. Probing Neil’s brain (Ojemann)  Aim: to localize functions  Area activated – “size of pencil eraser” I.e., about 1 sq cm Number of neurons under 1 sq cm of cortical surface: 14,000,000  Test for “naming sites” Problem

10. “Naming sites” found in Neil’s brain

11. Probing Neil’s brain – “Naming sites”  Problems with “naming sites” Naming is a complex function  Therefore, not localizable Ojemann doesn’t distinguish different kinds of objects  Additional problem in interpreting results: Input for testing is only pictures – visual stimuli Same problem comes up with results of many imaging studies

12. “Naming sites” identified in the experiment 1. In Broca’s area 2. In Wernicke’s area 3. In supramarginal gyrus N.B.: Angular gyrus not considered Was not under the section of skull removed Probably also involved

13. “Naming sites” – English and Spanish

14. Methods of localization  Lesion studies The traditional method For a long time, the only method  Selective anesthetization  Intra-operative mapping Started by Penfield and Roberts, 1960’s  Transcranial magnetic stimulation (TMS) Recently developed Very promising  Functional brain imaging Currently very popular Many techniques

15. Transcranial Magnetic Stimulation - TMS  Magnetic stimulation disrupts electrical activity  TMS disrupts activity only while it is being applied Recovery is immediate  Can induce temporary dysfunction of specific areas – e.g. Broca’s area  Usefulness depends greatly on areal precision, a function of expense

16. Methods of localization  Lesion studies The traditional method For a long time, the only method  Selective anesthetization  Intra-operative mapping Started by Penfield and Roberts, 1960’s  Transcranial magnetic stimulation (TMS) Recently developed Very promising  Functional brain imaging Currently very popular Many techniques

17. Brain imaging and functional brain imaging  Brain imaging Gets static image of brain structure Used for example in locating lesion areas E.g. MRI Exciting new development: DTI  Functional brain imaging Images of brain performing more or less specific function  E.g., linguistic, motor, sensory, attention  That is the ideal, never actually realized E.g. fMRI

18. Functional Brain Imaging Techniques  Electroencephalography (EEG)  Positron Emission Tomography (PET)  Functional Magnetic Resonance Imaging (fMRI)  Magnetoencephalography (MEG) Magnetic source imaging (MSI)  Combines MEG with MRI

19. Spatial and Temporal Resolution  Spatial resolution How accurately is location determined? Recall: 14,000,000 neurons under 1 sq cm of cortical surface Worst: EEG Best: MEG  Temporal resolution Accuracy in determining timing of activity Key neural events can occur within 5 ms Terrible: PET Pretty bad: fMRI Excellent: MEG and EEG

20. Electroencephalography (EEG)  An old technique, from the days before mapping techniques were developed Was used for recording brain wave activity, rather than for imaging  Any neuronal activity in the brain generates electric current flow  Current flows through the cranium and scalp  The changes in electric potential are detected by electrodes placed on the scalp

21. EEG Mapping  Nowadays multiple electrodes can be placed all over the scalp, allowing the recording of the electric activity from many different sites simultaneously  Allows the construction of topographic maps of the momentary electric activity on the scalp i.e., excellent temporal resolution  Also permits study of the time series of these maps with millisecond resolution But very poor spatial resolution

22. Multiple electrodes for mapping http://brainmapping.unige.ch/researchtopics.php

23. ERP Mapping  ERP – event related potentials  Traditional analysis: ERP waveforms at certain electrode positions  ERP mapping attempts to determine points in time when map configurations change and/or when they differ between experimental conditions  Relies on the fact that, whenever the spatial configuration of the electric field on the scalp differs, different neuronal populations are active in the brain, reflecting an alteration of the functional state of the brain Christoph M. Michel, Margitta Seeck and Theodor Landis, Spatiotemporal Dynamics of Human Cognition News Physiol. Sci 1999 Oct, 14:206-214

24. EEG-MRI Coregistration  Separate MRI images are taken  Reference points are used to get same positioning Impossible to get them accurate  But can get within a few mm

25. EEG-MRI Co-registration Spinelli L, Gonzalez Andino S, Lantz G, Seeck M, Michel CM. Electromagnetic inverse solutions in anatomically constrained spherical head models. Brain Topography 2000; 13: 115-126.Spinelli L, Gonzalez Andino S, Lantz G, Seeck M, Michel CM. Electromagnetic inverse solutions in anatomically constrained spherical head models. Brain Topography 2000; 13: 115-126.

26. Some Properties of EEG-ERP Mapping  Spatial resolution: Very approximate The volume currents picked up by the EEG electrodes are distorted as they pass through cranium and scalp [see next slides] Hence, imperfect correspondence between surface distribution and primary activation 2 nd problem: inverse dipole modeling  With multiple dipoles, impossible to get a unique solution  Temporal resolution: Excellent

27. Detecting electrical activity  Activation of neural fibers is electrical activity  Most fibers are too short to produce detectable signal even when active Relatively longer fibers:  Apical dendrites of pyramidal neurons  Cortico-cortical axons

28. Dipoles  The activity of a single fiber is too weak to be detected Therefore we need multiple parallel fibers acting in concert  Sets of neighboring apical dendrites firing synchrounously  Such a set, when active, constitutes a dipole

29. Source and volume currents Papanicolaou 1999: 32 Dipole Secondary currents shown in white

30. Volume Currents  Volume currents (read by an EEG) become distorted as they follow lines of least electrical resistance  Flow through layers of tissue offering different degrees of resistance (e.g., white matter, gray matter, meninges, cerebrospinal fluid)  Become further distorted by the skull, which provides the most resistance where it is thicker

31. Positron emission tomography (PET)  Tomography: Pictures (graph) of slices (tomo)  Positron emission: The pictures of brain activity result from emission of positrons Positron  Subatomic particle with very short half life  Like an electron but with opposite charge As soon as an emitted positron meets an electron, they annihilate each other and a photon is produced The photon is detected by the PET machine

32. Axial sections: commonly used in brain imaging “From the top/bottom” Accomplished by use of computerized tomography http://www.indiana.edu/~m555/axial/axial.html

33. PET Machine http://www.radiologyinfo.org/content/petomography.htm

34. In a PET Machine http://en.wikipedia.org/wiki/Positron_Emission_Tomography

35. Positron Emission Tomography (PET)  Measures the distribution of particular organic molecules and compounds (e.g., water, glucose, neurotransmitters) in the brain  The organic molecules and compounds are not detectable because they do not emit electromagnetic signals  Positron-emitting isotopes of these organic molecules and compounds are introduced into the blood intravenously It is necessary to have a cyclotron adjacent to the PET facility to produce the radioactive isotopes  After a short time period, the isotopes are dispersed throughout the brain

36. Positron Emission Tomography (PET)  These isotopes (in the blood) flow to the areas of the brain with the highest metabolic needs  These areas are assumed to be the most active at the given point in time  The positrons from the isotopes collide with electrons  These collisions produce photons, which can be detected at the surface of the head  The greater the activation of an area, the more positrons originate from that area

37. Positron Emission Tomography (PET)  Tomography is accomplished by computer using sophisticated algorithms  The final PET images show areas of different hues, each hue representing a different degree of activation of the underlying brain structures  The final PET images are superimposed on a structural image of the brain (MRI or CT scan)

38. Some PET Images PET images courtesy of UCLA Department of Molecular and Medical Pharmacology © 1995-2005, Healthwise, Incorporated, P.O. Box 1989, Boise, ID 83701. All Rights Reserved.

39. More PET Images http://encarta.msn.com/media_461519549_761555359_-1_1/Positron_Emission_Tomography.html

40. Some properties of PET  Spatial resolution: 5-10 mm  How good is that? Under one sq mm of cortical surface  130,000 neurons  1400 minicolumns (at est. avg. 93 neurons/col)  Temporal resolution: “…on the order of minutes…” (A. Papanicolaou, Fundamentals of Functional Brain Imaging (1998), p. 14)

41. PET study of object categories Hanna Damasio, Thomas Grabowski, Daniel Tranel, Richard Hichwa, Antonio Damasio, A neural basis for lexical retrieval. Nature 380, 11 April 1996, 499-505 Different categories of concrete objects found to be represented in different extrasylvian areas of left hemisphere. Both normal subjects and those with brain damage were tested. Categories tested Animals Tools Unique persons E.g., J.F.K.

42. Subjects, method, and findings  127 subjects with focal brain lesions Category-related defects correlate with different neural sites  9 normal subjects, tested with PET Differential activation of left temporal sites comparable to those of the lesion study  Method: visual naming experiment Three categories: tools, animals, unique persons

43. Patients with defects in more than one catetory  If two categories had defects, they were Animals and tools or Animals and unique persons  If both tools and persons affected, then animals were also  Q: What do these findings suggest?

44. Deficits vis-à-vis areas of damage  Abnormal access for names of unique persons correlated with damage in left temporal pole  Abnormal access for names of animals correlated with damage in left infero-temporal area  Abnormal access for names of tools correlated with damage in posterolateral inferotemporal and temporo-occipito-parietal junction area

45. Similar results from PET experiment on normal subjects  Increased rCBF (regional cerebral blood flow) in left temporal pole for naming unique persons  Some increase of rCBF also in right TP for naming unique persons  Animals and tools activated left posterior inferotemporal areas, more posterior for tools

46. Functional Magnetic Resonance Imaging (fMRI)  Measures the amount of oxygenated blood supplied to different areas of the brain Common abbreviation: rCBF (regional cerebral blood flow)  When a group of neurons increases its signaling rate, its metabolic rate increases  When the metabolic rate increases, the amount of hemoglobin in the blood decreases Since brain metabolism requires oxygen Hemoglobin is the protein that delivers oxygen to body tissues (Also collects CO 2 )

47. Functional Magnetic Resonance Imaging (fMRI)  The decrease in hemoglobin becomes apparent approximately 2 seconds after the increase in the neurons’ signaling rate  Then, oxygenated blood flows into the depleted area, resulting in excessive amounts of hemoglobin in the area This flood of oxygenated blood to the depleted area occurs 5 to 8 seconds after the low level of hemoglobin is detected

48. Functional Magnetic Resonance Imaging (fMRI)  The fMRI results are superimposed on a structural MRI

49. MRI Machine http://www.radiologyinfo.org/photocat/photos.cfm?Image=philips5.jpg&&subcategory=Brain

50. Another MRI Machine http://www.radiologyinfo.org/photocat/photos.cfm?Image=hitachi.jpg&&subcategory=Brain

51. fMRI properties  Temporal resolution: not very good  Image reflects the increase in oxygenated blood that occurs 5 to 8 seconds after the neurons fire  Records all activation that occurs within the recording interval; does not separate early versus late activation  For example, there is no way to separate activation of, for example, primary auditory cortex and higher-level association cortices during a process of speech comprehension

52. fMRI: Example http://www.fmrib.ox.ac.uk/fmri_intro/fusion.gif

53. Another example www.firstscience.com/ SITE/ARTICLES/love.asp Areas of the brain used in working memory

54. Properties of fMRI  Spatial resolution: good  However, it is unclear whether the imaged area is precisely the area involved in the activity The flow of oxygenated blood into the depleted area may also flow into neighboring vessels in areas where neural firing did not occur (next slides)

55. Active area

56. Area that “lights up” in fMRI (hypothetical example) Active area

57. Functional Brain Imaging Techniques  Electroencephalography (EEG)  Positron Emission Tomography (PET)  Functional Magnetic Resonance Imaging (fMRI)  Magnetoencephalography (MEG) Magnetic source imaging (MSI)  Combines MEG with MRI REVIEW

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