The Tools: Imaging the Living Brain

Transcription

1 The Tools: Imaging the Living Brain I believe the study of neuroimaging has supported the localization of mental operations within the human brain. -Michael I. Posner, 2003

2 Neuroimaging methods Since Descarte mind vs body materialism what does the brain have to do with it? NEURO COGNITIVE GAP: Cells Fires > We Order Lunch

3 System level brain measures: Brain Imaging 1990s Brain Imaging technologies began to appear New Field emerged: Cognitive Neuroscience Promise: to look inside brain and see the underlying processes.

4 Neurons are Information Processing Structures

5 Integrate and Fire!

6 MOST NI Above Here

7 The time-space tradeoff: some techniques provide high temporal resolution of brain activity (such as EEG) while others provide higher spatial resolution (such as fmri).

8 Brain recording: more and less direct measurements How do brain recordings reflect human cognition? While they are indirect measures, each type of brain recording tells us part of the story of how the brain works. Here is an image of the brain using diffusion tensor imaging: this technique allows us to view white (myelinated) fiber tracts.

9 A range of useful tools -measuring electric and magnetic signals Single-unit recording: Recording from individual neurons can tell us about spiking patterns in the brain. Here you see that the activity in this single unit is most active (shown in red) during the delay period. Such neurons are thought to be involved in the working memory system.

10 A range of useful tools -Homologies Animal and human studies cast light on each other Some macaque behaviors are similar to humans as well, such as close infant-mother bonding.

11 A range of useful tools -Homologies Animal and human studies cast light on each other While humans and monkeys are very different, some monkeys, such as the macaque, are extensively studied because of the similarity between their brains and human brains. Human Macaque

12 A range of useful tools -measuring electric and magnetic signals Electroencephalography (EEG) recordings reveal brain rhythms such as Gamma (40Hz). Gamma activity is thought to signal exchange of information between cortical and subcortical regions.

13 A range of useful tools -measuring electric and magnetic signals Magnetoencephalography (MEG) MEG recordings reflect magnetic -- not electric -- cortical activity. MEG has higher source localization capabilities than EEG.

14 A range of useful tools -measuring electric and magnetic signals Zapping the brain -- Transcranial Magnetic Stimulation (TMS) TMS uses brief magnetic pulses over the scalp to inhibit or excite a small region of cortex. TMS is used to test causal hypotheses about the contribution of specific brain regions to complex cognitive processes.

15 3.0 fmri and PET: indirect signals for neural activity fmri provides a measure of hemodynamic (blood based) activity in the brain and is based on the premise that neuronal activation increases oxygen demand of neurons and related cells, leading to additional blood flow carrying oxygen molecules to the region. This can be measured using BOLD -- Blood Oxygen Level Dependent -activity. fmri is the dominant neuroimaging technique today in research.

16 MRI studies brain anatomy. Functional MRI (fmri) studies brain function.

17

18 fmri Setup /home/jose/courses/scanner2.wav

19 Getting fmri Data Like a human Radio 1) Put subject in big magnetic field (leave him there) 2) Transmit radio waves into subject [about 3 ms at a specific frequency] 3) Turn off radio wave transmitter 4) Receive radio waves re transmitted by subject Manipulate re transmission with magnetic fields during this readout interval [ ms: MRI is not a snapshot] 5) Store measured radio wave data vs. time Now go back to 2) to get some more data 6) Process raw data to reconstruct images (Fourier

20 fmri depends on 3 lucky aspects of the human body 1. We're mostly made out of Water allowing for magnetic succesptibility in tissue (Protons) 3. Changes in neural activity produce changes in local blood flow 4. Local blood flow disrupts local tissue magnetic succeptibility allowing for localization

21 Protons Align in Magnetic Field Outside the Magnet Inside the Magnet M Brain is 70% water High abundance of H protons throughout tissue. When placed in a Magnetic Field (50k times> Earth's) Protons in the brain begin to align in particular HYDROGEN Protons A radio frequency Pulse at the frequency of the HYDROGEN PROTON (170.3 MHz) which perturbs the alignment and then slowly relaxes back to the aligned state: TIME CONSTANT T1

22 T1 and TR T1 = recovery of longitudinal (B0) magnetization used in anatomical images ~ msec (longer with bigger B0) TR (repetition time) = time to wait after excitation before sampling T1 Different Tissue have different T1 time constants.. CSF is slow 3seconds, white matter 500ms

23 Magnetic Susceptibility Impurities in the Magnetic Field Proton effect Homogenous Unless for some reason Brain is locally perturbed Neural Activity > produces Oxygen Consumption Blood Flow to local area to replenish Oxygen brings oxyhemoglobin (oxygen loaded hemoglobin) which is paramagnetic hence producing a local disturbance in the magnetic field (a NATURAL CONSTRAST AGENT) changes in Magnetic Susceptibility to surrounding tissue. Thus producing SLOWER Time Constants for the surrounding tissue and hence a STRONG MR SIGNAL (T2*) perturbance magnetic susceptibility

24 BOLD Genesis T2* is the decay due to local perturbance of magnetic field We have no idea how this happens

25 Ideal HDR The peak to optimize for Brain mapping sometimes called the task area. 6 8 seconds from neuronal event 0 0 Seconds % signal change = (point baseline)/baseline 20 time to rise signal begins to rise soon after stimulus begins usually 0.5 3% could be as high as 10% initial dip more focal and potentially a better measure time to peak signal peaks 4 6 sec after stimulus begins post stimulus undershoot

26 Properties of BOLD susceptibility of brain tissue The statistical interpretation of signals in BOLD* involve (1) the noise model for the signal: this effects detection, interpretation of the number of relevant areas, patterns of effects and the potential shape and size of the tissue sensitive to the measurement. (2) the impulse response temporal dynamics. Identifiabilty is critical in determining the temporal properties of the measurement

27 Despite lack of Identifiability: HRF Convolution is useful for maximizing signal Experimental Stimulus Function Hemodynamic Response Function Predicted Response Block Design Event Related

28 OVERVIEW OF BRAIN IMAGING ANALYSIS

29 Finger tapping

30 MRI vs. fmri high resolution MRI fmri (1 mm) low resolution (~3 mm but can be better) one image fmri many images Blood Oxygenation Level Dependent (BOLD) signal indirect measure of neural activity neural activity (e.g., every 2 sec for 5 mins) blood oxygen fmri signal

31 fmri Activation: AVERAGING Source: Posner & Raichle, Images of Mind

32 Slice Terminology VOXEL Slice Thickness (Volumetric Pix In plane resolution e.g., 6 mm e.g., 192 mm / 64 = 3 mm SAGITTAL SLICE IN PLANE SLICE Number of Slices e.g., 10 Matrix Size e.g., 64 x 64 Field of View (FOV) e.g., 19.2 cm 3 mm 3 mm

33 Activation Statistics Functional images ROI Time Course fmri ~2s Signal (% change) Time Co nd it ion Condition Statistical Map 1 superimposed on anatomical MRI image Time Co nd itio Region of interest (ROI) n 2... ~ 5 min

34 Statistical Maps & Time Courses Then extract the time course Use stat maps to pick region

35 What are the temporal limits? What is the briefest stimulus that fmri can detect? Blamire et al. (1992) 2 sec Bandettini (1993): 0.5 sec Savoy et al (1995): 34 msec With enough averaging, anything seems possible. The shape of the HRF is predictable. Event related potentials (ERPs) are based on averaging small responses over many trials.

36 Subject Safety Anyone going near the magnet subjects, staff and visitors must be thoroughly screened: Subjects must have no metal in their bodies: pacemaker aneurysm clips metal implants (e.g., cochlear implants) interuterine devices (IUDs) some dental work (fillings okay) Subjects must remove metal from their bodies jewellery, watch, piercings coins, etc. wallet This subject was wearing a hair band with a ~2 mm copper clamp. Left: with hair band. Right: without.

37 fmri and PET: indirect signals for neural activity Regions of interest: The brain is a dynamic, complex entity. How do you know which brain activity corresponds to your research experiment? One technique is to define regions of interest (ROIs) before scanning to identify which areas you expect to see changes in activation.

38 1.0 Introduction The geography of the brain The four major lobes of the brain are visible from a lateral view. A lateral view of the left hemisphere, with the frontal lobe (purple) at the anterior of the brain, the parietal lobe (orange) posterior to the frontal lobe at the superior aspect of the brain, the temporal lobe (blue) posterior to the frontal lobe and inferior to the parietal lobe, and the occipital lobe (yellow) which is posterior to both the parietal and temporal lobes.

39 1.0 Introduction The geography of the brain Some important landmarks of the brain in the left hemisphere from a lateral perspective (left panel) and a mid-sagittal perspective (right panel).

40 The geography of the brain A schematic drawing of the six layers in the gray matter of the cortex. Some cortical neurons send their axons to the thalamus, while others receive input from thalamic neurons.

41 1.0 Introduction The geography of the brain The Brodmann classification (based on microscopic cell differences) of regions in the left hemisphere, shown in a lateral view. Areas 41 & 52 are indicated by lines. Some areas, like the insula and auditory region, are tucked away behind the temporal lobe.

42 1.0 Introduction The geography of the brain The Brodmann classification of regions in the left hemisphere in midsagittal view.

43 Growing a brain from the bottom up Building a brain from bottom to top The brain builds on the brainstem, with the thalami on top as a major input hub. The hippocampi and amygdalas are actually nestled inside each of the temporal lobes. The light blue ventricles have no neurons, but provide the brain s own circulatory system. The basal ganglia can be thought of as the output hub of the system. A great deal of traffic flows back to the cortex as well.

44 3.0 From where to what : the functional roles of brain regions Output and input: the front-back division The frontal lobe typically is involved in executive and motor (output) functions. The posterior half of the brain is involved in sensory processing. A view of functional areas in sensory regions of the cortex: the central sulcus separates the frontal lobe from the parietal. Immediately anterior to the central sulcus are motor areas, and just posterior to the central sulcus is the primary somatosensory area.

45 From where to what : the functional roles of brain regions Output and input: the front-back division A homonculus ( little man ) shows the body map for motor representation of different areas of the body. Note that some body areas, such as the fingers, have disproportionately larger representation than other body areas, such as the trunk.

46 From where to what : the functional roles of brain regions Output and input: the front-back division A homonculus ( little man ) shows the body map for somatosensory representation of different areas on the body. Note that some body areas, such as the face, have disproportionately larger representation than other body areas, such as the trunk.

47 The Little Man in the somatasensory cortex

48 From where to what : the functional roles of brain regions Output and input: the front-back division The close physical connection between motor cortex, located just anterior to the central sulcus, and the somatosensory cortex, located just posterior to it, allows for a tight coupling between the senses of touch, pressure, and pain and the action or motor system.

49 fmri and PET: indirect signals for neural activity The resting brain is not silent Many fmri and PET research protocols subtract an experimental condition from a baseline -- frequently a resting state where the subject does not have a task to perform. But, is the brain resting? While activity during a resting state may not be directly related to the tasks being performed in other states, we know that humans are constantly thinking, imagining, feeling, anticipating and remembering. Background activity in the left and right hemispheres during a resting state

50 4.0 Conscious and unconscious brain events A recent wave of brain studies are investigating conscious and unconscious phenomena in the brain. For example, a fmri study compared brain activation for conscious and unconscious events: unconscious viewing of words activated visual areas only, while conscious viewing activated expanded regions in the cortex.

51 Pessoa: Fear recognition..

52 Correlation and Causation Brain damage and causal inferences Brain injuries can provide evidence that areas are necessary for certain cognitive functions, however it is important to keep in mind that studies of brain-damaged individuals provide correlational, not causal, explanations about brain function.

53 Summary The advent of brain imaging has transformed the study of human cognition. New and refined methods are constantly being produced. There is a wide array of methods and techniques for brain recording: brain imaging techniques allow us measure single neurons as well as large cortical activations, brain structures as well as dynamic brain activity. A powerful use of brain imaging is to provide converging evidence, across techniques and research populations, to better understand human cognition.