1. Functional MRI David Card

2. fMRI So what exactly are we measuring in fMRI? Our goal is to “see” neural activity We are actually seeing changes in blood flow The idea is based off of differing magnetic properties of oxygenated blood and deoxygenated blood Oxygenated blood is diamagnetic Deoxygenated blood is paramagnetic This difference creates a contrast termed BOLD (blood oxygen level dependent)

4. From Action Potential to BOLD Signal Action potential down an axon induces the release of neurotransmitters into the synapse One of the neurotransmitters released in glutamate Glutamate is taken up by surrounding astrocytes Once the astrocyte takes up glutamate it causes the astrocyte to release nitric acid Nitric acid is a vasodilator and causes the dilation of near by vasculature Dilated blood vessels cause an increase in blood flow to the region An increase in blood flow causes an increase in BOLD signal

5. The Physics

6. The Physics Continued

7. From the Math to the Image We are measuring S We want to know ΔY, the change in hemoglobin oxygen level During an increase in neural activity the body over compensates and sends an excessive amount of oxygenated hemoglobin Therefore ΔY>0 implies an increase in neural activity. To produce an image one takes a normal MRI (baseline) then overlays the information from the ΔY.

8. Example Red areas refer to positive ΔY Blue areas refer to negative ΔY Note that the physiology corresponding to negative ΔY is not well understood since the active inhibition of neurons requires the firing of nearby inhibitory neurons

9. Some limitations Time Physical – limitations of the machine to take sequential images Biological – The time delay between neuron firing and time it takes for the oxyhemoglobin concentration to increase Spatial - Hemodynamic response is a global reaction and not necessarily pinpointed to the neurons that caused the response Signal to Noise – Due to the wide range of activities happening in the brain at any given moment caused by a multitude of stimuli it is difficult to hear the signal you are looking for over the noise of other neurons Logistics – What functional tests can be completed while inside an MRI machine.

10. Neural Decoupling Study done here at Penn State showing that there are instances of neural activity without a hemodynamic response Study done in mice walking on a treadmill with implanted electrodes in the somatosensory and motor cortices and a cranial window Idea is that while walking your brain increases activity in the motor cortex, telling your legs to move, while simultaneously receiving feedback to the somatosensory cortex, feeling the ground beneath you. The study found that there was increase in neural activity in both cortices however there was a hemodynamic response to the somatosensory cortex but not in the motor cortex

11. Neural Decoupling Continued This phenomena is not well understood yet but it is believed that different regions of the brain have differing thresholds before a significant hemodynamic response occurs

12. Clinical Applications Neurosurgical Planning Psychiatry Memory/Dementia Epilepsy

13. Neurosurgical planning

14. Neurosurgical Planning Continued Patient from previous slide presented following the occurrence of a seizure. Conventional MRI image revealed a mass in the motor cortex (Figure A). Due to the risk to motor and sensory function a seizure management plan was suggested. The patient sought a second opinion at a facility with fMRI capabilities. The fMRI showed that the tumor displaced functional areas (Figure B). With precise knowledge of the critical functional areas a surgical plan was devised to completely remove the tumor and at six months functionality had returned to normal (Figure C).

15. Psychiatry Developmental disorders – Autism Substance abuse and dependence Schizophrenia Mood Disorders An important consideration when performing fMRI test on patients with psychiatric conditions is how being in an MRI machine may exacerbate their condition and effect the results of the fMRI

16. Autism Research showing the differing pathways for information processing in healthy (top) and autistic patients (bottom)

17. Substance Abuse and Dependence fMRI is used to research specific brain regions effected by chronic drug use. The figure at the right show the effects of chronic marijuana use when performing a memory task. Healthy subjects top and chronic users bottom

18. Schizophrenia fMRI has been used to study the differences in neural activities in schizophrenic patients. The figure to the right shows the functionality of a schizophrenic patient while performing a finger to thumb task. The fMRI shows a significant decrease in neural activity in both the somatosensory and motor cortices in schizophrenic patients as compared to healthy patients

19. Mood Disorders Research has been done using fMRI in patients with major depression and bipolar disorder The figure on the right uses fMRI to study the differences in neural activity in reaction to faces of fear (top) and happy (bottom) both images show the increase in activity of control subjects over those of depressed patients