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Behavioral Neuroscience & Neurology • Lesion studies – Animals – Patient case studies • Phineas Gage • H.M. • Single cell recordings • Behavioral studies • TMS (Transcranial Magnetic Stimulation) – Creating artificial & temporary lesions in the brain Transcranial Magnetic Stimulation (TMS) Cognitive Neuroscience STRUCTURAL Neuroimaging – CT (Computerized Tomography) – MRI (Magnetic resonance imaging) • 3-D combine x-ray or MRI slices FUNCTIONAL Neuroimaging – EEG (Topography) 1929 • MEG (Magnetoencephalogram) – PET (Positron Emission Tomography – 1970s) • cerebral glucose levels • high spatial resolution but low temporal and invasive – fMRI (functional MRI) – 1990s functional Magnetic Resonance Imaging (fMRI) • Measures cerebral hemodynamic response (BOLD signal) – Blood flow in brain – levels of oxygen in (deoxy)hemoglobin recruited by firing neurons • Structure AND function in single scan – High spatial resolution with modest temporal resolution • Problem: loud scanner noises, machine artifacts MRI physics (1) Static magnetic field B0 is on B0 Water molecules align with B0 (equilibrium state) B0 (2) Magnetic field B1 is applied (orthogonal to B0 and at proton’s resonance frequency) Water molecules are “flipped” into excited state (not equilibrium) B1 (RF pulse) B0 (3) Relaxation (T1 and T2) Water molecules return to equilibrium state (this creates changing magnetic field) T1 (white matter) MR signal T1 time T2 Changing magnetic field creates current in the wire loop which can be measured Fourier Transform MR signal B0 (4) NMR signal detection T1 (gray matter) T2 (gray matter) T2 (white matter) Conventional MRI white matter gray matter • MRI is sensitive to myelin HIGH Spatial Resolution of MRI MRI Histology Layer IV MRI vs. fMRI MRI - shows difference between different types of tissues (“difference in space”, e.g. white vs. gray matter) fMRI -shows difference between stimulated and non-stimulated tissue (“difference in time”) What is functional MRI (fMRI)? Stimulus Off (Condition 1): Stimulus On (Condition 2): increased metabolism requires more oxygen MR signal T2 (stimulated tissue) more oxygen changes magnetic properties of the tissue T2 (tissue at rest) MR signal increases (S) S time • fMRI detects subtractive difference in signal (S = Cond. 2-Cond.1) • fMRI is indirect (hemodynamic) method of cellular communication Structural MRI & Anatomical MRI (T1-weighted) Functional MRI Structural MRI (gray matter thickness map) Functional MRI (activation to music) Diffusion Tensor MRI (white matter tracts) Spatio - temporal scales Spatial Resolution (mm) 10 8 6 MEG / EEG PET 4 fMRI 2 Single / Multi Unit Recording 0 1 msec 1 sec 1 min 10 min 1 hour Temporal Resolution (sec) Why fMRI? • non-invasive => can be used in humans • measures population neural activity • can study whole brain at once MRI scanner Magnetic field: • is VERY STRONG ( 3T ~ 30,000 times the earth’s magnetic field) • is ALWAYS ON Image Artifacts and Subject Safety With hair band Without hair band Typical fMRI experiment Stimulus Stimulus Stimulus Stimulus (30 s) (30 s) (30 s) (30 s) Off Stimulus (e.g. music) is presented to subject repeatedly every 30 sec. • Images are acquired ~2 sec. • MR signal is estimated for every voxel as a function of time Off On ... 0 4 TIME (minutes) image acquired at each tick mark Image Intensity • On ... time • Change in MR signal between “On” and “Off” conditions is calculated for every voxel. • Voxels with significant change of the MR signal are displayed on the anatomical image. Scanner Noise • Scanner noise sources: – scanner cooling system (ongoing) – gradient coils (every image acquisition) • Noise is a PROBLEM: – want response to stimulus, get response to stimulus+scanner noise – scanner noise reduces dynamic range of response – scanner noise masks stimulus • Solutions: – blocking noise transmission to the subject (earplugs, earmuffs) – modifying scanner – modifying experiment Subcortical Activation MGB IC SOC CN Auditory Pathway Inferior Colliculus (sound intensity varied) 35 dB SL 55 dB SL 75 dB SL p = 0.01 p = 2 x 10-9 Inferior Colliculi Image Signal Change Sound On 1 0 0 30 0 30 0 30 Time (seconds) 1 Auditory Cortex music noise Percent Signal Change auditory cortex Sound On 0 30 Time (sec) 0 30 Time (sec) Millisecond changes in electrophysiology (ERPs) Functional Neuroimaging Resolution Spatial Temporal EEG/MEG 1-3 cm2 1 ms PET 3 mm3 20 s (+ 3-8 s lag) fMRI 1 mm3 2s (+ lag of 3-8 s) Dis/Advantages of each technique Mind vs Brain • VHS 1518.25 Dr Phil- Cognitive Neuroscience