Functional Brain Imaging (cont’d) MEG

1. Ling 411 – 10 Functional Brain Imaging (cont’d)MEG

2. REVIEW 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

3. Magnetoencephalography (MEG) MEG (MagnetoEncephaloGraphy) measures the magnetic field around the head Compare EEG: Measures voltage changes on the scalp MSI (Magnetic Source Imaging) is MEG coupled to MRI

4. Intra-Cranial Sources Dipole (source current) Papanicolaou 1998:31

5. Magnetoencephalography (MEG) Records the magnetic flux or the magnetic fields that arise from the source current A current is always associated with a magnetic field perpendicular to its direction Magnetic flux lines are not distorted as they pass through the brain tissue because biological tissues offer practically no resistance to them (cf. EEG)

6. A dipole is a small current source Dipole generates a magnetic field Dendritic current from apical dendrites of pyramidal neurons At least 10,000 neighboring neurons firing “simultaneously” for MEG to detect

7. Recording of the Magnetic Flux Recorded by special sensors called magnetometers A magnetometer is a loop of wire placed parallel to the head surface The strength (density) of the magnetic flux at a certain point determines the strength of the current produced in the magnetometer If a number of magnetometers are placed at regular intervals across the head surface, the shape of the entire distribution by a brain activity source can be determined (in theory)

8. Magnetic flux from source currents Magnetometer Magnetic flux Source current

9. Recording of Magnetic Signals

10. An MRI Machine

11. Recording of the Magnetic Flux Present day machines have 248 magnetometers The magnetic fields that reach the head surface are extremely small Approximately one million times weaker than the ambient magnetic field of the earth Because the magnetic fields are extremely small, the magnetometers must be superconductive (have extremely low resistance) Resistance in wires is lowered when the wires are cooled to extremely low temperatures

12. Recording of the Magnetic Flux When the temperature of the wires approaches absolute zero, the wires become superconductive The magnetometer wires are housed in a thermally insulated drum (dewar) filled with liquid helium The liquid helium keeps the wires at a temperature of about 4 degrees Kelvin The magnetometers are superconductive at this temperature

13. Recording of the Magnetic Flux The currents produced in the magnetometers are also extremely weak and must be amplified Superconductive Quantum Interference Devices (SQUIDS) The magnetometers and their SQUIDS are kept in a dewar, which is filled with liquid helium to keep them at an extremely low temperature

14. How a MEG Recording is Made The MEG machine is located in a magnetically shielded room Subjects cannot wear any metal because it affects the recording Digitization process After digitization, the task is run and the recording is made

15. The Digitization Process Needed for co-registration with MRI MRI scan is done later Provides images MSI – Magnetic Source Imaging Method 5 points 3 electrodes on forehead 2 earpieces Subjects must remain extremely still during the digitization process After digitization, the task is run and the recording is made

16. Dipolar Distribution of the Magnetic Flux In the following figure, one set of concentric circles represents the magnetic flux exiting the head and the other represents the re-entering flux This is called a dipolar distribution The two points where the recorded flux has the highest value are called extrema The flux density diminishes progressively, forming iso-field contours

17. Surface distribution of magnetic signals Extrema

18. Dipolar Distribution of the Magnetic Flux From the dipolar distributions, we can determine some characteristics of the source The source is below the mid-point between the extrema (points where recorded flux has highest value) The source is at a depth proportional to the distance between the extrema Extrema that are close together indicate a source close to the surface of the brain A source deeper in the brain produces extrema that are further apart The source’s strength is reflected in the intensity of the recorded flux The orientation of the extrema on the head surface indicates the orientation of the source

19. Co-registration of MEG and MRI space

20. MEG scan co-registered with MRI scanusing fiducial markers

21. Result of co-registration

22. Event-related brain responses: EEG & MEG Both types of signals come from the same type of event: active dipoles Different directions from the dipoles Detected by different devices With EEG ERP – event-related potential With MEG ERF – event-related (magnetic) field Addition from 100 or more trials for each tested condition needed to get measurable data

23. The inverse problem A problem for EEG and MEG Locating the dipole(s) based on signals reaching surface of scalp Problem: Multiple solutions are possible Cf. solving x + y = 24 Computer uses iterative procedure to come up with best fit The problem is compounded by the fact that the brain is a parallel processor Many dipoles at each temporal sampling point

24. Testing Reliability of MSI Necessary in early stages of research Does MEG give reliable localization results? Compare with results of Wada test Excellent correlations found (But this tests only very crude localization) Compare with results of intraoperative mapping MSI and mapping by cortical stimulation demonstrate similar localization abilities –excellent correlation

25. MSI before neurosurgery MSI is preferred because mapping by cortical stimulation increases the patients’ susceptibility to infections as a result of lengthened surgery durations MSI can be performed prior to the scheduled surgery so that the surgeons can plan the best way to remove the damaged area while avoiding language areas as best they can

26. Temporal Resolution of MEG Excellent – unlike fMRI and PET The temporal order of activation of areas in a pattern can be discerned The time course of the activation can be followed MEG has potential to detect the activation of several brain regions as they become active from moment to moment during a complex function such as recognition

27. Temporal Resolution of MEG Only with MEG can we detect the activation of several brain regions as they become active from moment to moment during a complex function such as recognition But it is (at present state of the art) virtually impossible to achieve precision

28. Time course of activation We can follow the activation of a source across time The magnetic fields recorded in MEG are evoked Activation at each point in time is recorded (millisecond sensitivity) Sources of early components of Evoked Fields circumscribe the modality-specific sensory areas Sources of late components circumscribe different sets of brain regions (mostly association cortex) These activation patterns are function- (or task-) specific

29. Spatial limitation of MEG Magnetic flux is perpendicular to direction of electrical current flow Flux is therefore relatively easy to detect if dendrites are parallel to surface of skull i.e., for pyramidal neurons along the sides of sulci But hard or impossible to detect if vertical i.e., for pyramidal neurons at tops of gyri or at bottoms of sulci

30. The challenge of MSI The cortex is a parallel processor Hundreds or thousands of dipoles can be active simultaneously Multiple dipoles make comprehensive inverse dipole modeling virtually impossible Hence, compromises are necessary Sample larger time spans (up to 500 ms) Sample larger areas (up to several sq cm)

31. Some MEG/MSI Findings

32. Speech recognition: MEG results Hemispheric Asymmetry Wernicke's Area

33. Variability in location of Wernicke’s area(different subjects) From MEG lab, UT Houston

34. Wernicke’s area in bilinguals From MEG lab, UT Houston

35. Localization of phonemes:The claim of Obleser et al. • Different locations (in temporal lobe) for different vowels • The anterior-posterior axis corresponds to the backness of a vowel – the more back the vowel, the more posterior the source location • The superior-inferior axis corresponds to the height of a vowel (inverse relationship) – the higher the vowel, the more inferior the source location of that vowel From: Ladefoged, P. (2001). Vowels and Consonants: An Introduction to the Sounds of Languages. Malden, Massachusetts: Blackwell Publishers, Inc.

36. Distinguishing features of vowels Tongue positions • Tongue height corresponds to F1 (first formant) • Front-back dimension corresponds to F2 (2nd) • The formants are detected in auditory processing (upper temporal lobe) • Tongue positions are controlled by motor cortex (frontal lobe) and monitored in parietal lobe From: Ladefoged, P. (2001). Vowels and Consonants: An Introduction to the Sounds of Languages. Malden, Massachusetts: Blackwell Publishers, Inc.

37. MEG and localization of phonemes Wernicke’s area may be organized phonemotopically The anterior-posterior axis corresponds to the backness of a vowel – the more back the vowel, the more posterior the source location The superior-inferior axis corresponds to the height of a vowel (inverse relationship) – the higher the vowel, the more inferior the source location of that vowel From: Ladefoged, P. (2001). Vowels and Consonants: An Introduction to the Sounds of Languages. Malden, Massachusetts: Blackwell Publishers, Inc.

38. MEG and localization of phonemes Results: The relative positions of neural representations for vowels in Wernicke’s area correlate with the relative positions of the vowels in articulatory space Obleser, Elbert, Lahiri, & Eulitz, 2003 Obleser, Lahiri, & Eulitz, 2004 Obleser, Elbert, & Eulitz, 2004 Eulitz, Obleser, & Lahiri, 2004 Can this finding be replicated? Finding supported by different lab! Shestakova, Brattico, Soloviev, Klucharec, & Huotilainen, 2004!

39. Shestakova et al. experiment (2004) • Done in Helsinki, Russian vowels [i a u] • Obleser et al. in Germany, German vowels [i a u] • Results similar to those of Obleser et al. • Higher cortical location for [a] • Front-back cortical location corresponds to articulatory positions • They go two steps further: • Input from different speakers (all male) • Similar findings in both LH and RH

40. An MEG study from Max Planck Institute Naming animals from visual (picture) input LH RH

41. More information on MEG The University of Texas Health Science Center at Houston Division of Clinical Neurosciences MEG Lab: http://www.uth.tmc.edu/clinicalneuro/ Papanicolaou, A. (1998). Fundamentals of Functional Brain Imaging: A Guide to the Methods and their Applications to Psychology and Behavioral Neuroscience.Lisse: Swets & Zeitlinger.

42. Imaging methods compared

43. A practical consideration: Cost Most expensive: MEG About $2 million for the machine $1 million for magnetically shielded room Next most expensive: PET Next: fMRI Cheapest: EEG

44. Temporal resolution – summary PET: 40 seconds and up fMRI: 10 seconds or more MEG and EEG: instantaneous Theoretically it is possible to do ms by ms tracking, to follow time course of activation Commonly used sampling rate for MEG: 4 ms Practically, such tracking is difficult or impossible The inverse problem Too many dipoles at each point in time

45. Spatial Resolution • EEG: Poor • PET: Fair – 4-5 mm • fMRI: Fair – 4-5 mm • MRI: Good – 1 mm or less • MEG: Fairly good – 3-4 mm or less • Under good conditions

46. Sensitivity of Imaging Methods All of the methods have limited sensitivity MEG 10,000 dendrites in close proximity have to be active to detect signal PET and fMRI Similar limitations Any activation that involves fewer numbers goes undetected

47. The Territory of Neurolinguistics:An Intellectual Territorywith three dimensions

48. Dimension 1: Size Dimension 2: Static – Dynamic D y nami c m a j o r s t r u c t u r a l c h a n g e s m a l l s t r u c t u r a l c h a n g e f u n c t i o n / o p e r a t i o n a n a t o m i c a l s t r u c t u r e s Static 1 10 100 1 10 100 1 1 10 - - - - - nm - - - - - - - - - - - μm - - - - - mm - - cm - -

49. Tiny sizes – nm to μm range Synaptic Structure

50. Small sizes – μm range • Pyramidal cell • Diameter of cell body: 30-50 μm • Diameter of axon: up to 10 μm • Diameter of apical dendrite: up to 10 μm • Cortical minicolumn • Diameter: 30-50 μm • Layers of the cortex • Average thickness of one layer: 500 μm