Origin of Negative BOLD fMRI Signals Norm Harel at al Presented by Hyunggoo Kim

History 1930 Dia/paramagnetic property of Oxy/deoxyheamoglobin 1952 Discovered NMR 1971 nuclear magnetic relaxation times of tissues and tumors differed 1982 blood oxygenation lead to decrease in T2, T2* NMR relaxation time of blood 1989 in vivo imaging in rat 1992, BOLD contrast by ogawa

TERM CBF: cerebral blood flow CBV: cerebral blood volumne CMR: cerebral metabolic rate

MRI (1) NMR(Nuclear magnetic resonance) Imaging technology Proton, neutron spins along strong magnetic field Spin frequency V = rB, r is specific for each atom Using H (H2O is abundant in body) High/low energy spin state Emiting electomagnetic wave (High to low)

MRI (2) Decaying time(T1,T2,T2*) varies along to environment (skeleton, tissue, etc) Detecting signal using coil by electomagnetic Induction Using constrast of signal strength for converting signal strength to visual graphic Various technique about How to evoke signal How to detect signal How to analyze data

fMRI Functional <-> anatomical Detect signal constrast between specific task Spatio-temporal difference of signal Correlate function achiving the task and the region of brain area

BOLD fMRI (1) Dia/Paramagnetic stuff change relaxation time Oxygen + Fe (in Hb) : Diamagnetic (Deoxy) + Fe (in Hb): Paramagnetic Paramagnetic makes magnetic field inhomogeneous Decay time prolonged in inhomogeneous M.F. What cause deoxy ? C6H12O6 + 6O2 -> 6CO2 + 6H20 (Glycolysis) mainly in neurotransmitter metabolism So, Neural activity is related But much argument about precise mechanism CBV, CBF, etc.. time strength

BOLD fMRI (2) 1st phase 2st phase 3st phase More deoxy -> more paramagnetic -> inhomogeneous magnetic field -> T2 time shortened -> signal- 2st phase CBF >> oxygen demand -> T2 prolonged -> signal+ 3st phase CBF return, oxygen demand return, signal return

Experiment Overview Objective: Clarify BOLD mechanism Question: Negative BOLD mean decreased neuroal activity ? Input: square-wave grating stimulus Output: BOLD constrast Analysis: Cross-correlation method

Positive / Nagative BOLD V1 positive, Higher area negative

BOLD – CBV relation V1: TCBV < TBOLD Higher: TBOLD < TCBV

Discussion (1) V1 & Higher area are highly related At lower PCO2, BOLD response faster and no initial dip

Discussion (2) Common arterial branch share blood flow More active region can ‘steel’ blood flow from relatively less active region CBF may not explain all neuronal activation Despite of Increased neuronal activity, these region may not escape ‘initial dip’ state TCBV < TBOLD explains arterial expansion -> hemodynamic change

Conclusion Caution should be taken when interpreting negative BOLD signal