Sir Peter Mansfield Magne0c Resonance Centre University of Nongham, UK FP7 Neurophysics Workshop Pharmacological fMRI Warwick Conference Centre, 23 January 2012 Mul0modal approaches to funconal neuroimaging Peter Morris Functional MRI Functional CNR ΔS/N = SNR . ΔR2* / R2* 7T MPRAGE, 0.5mm isotropic resolution, SENSE factor 2, acquisition time 11 mins for the whole head ΔR2* maps as a funcon of strength -1 1.5T 5 s 0.39 s-1 3T 5 s-1 0.39 s-1 7T 5 s-1 0.39 s-1 Field dependence of ΔR2*/R2* Composite ROI Inclusion ROI 0.1 Composite ROI Inclusion ROI Composite 0.08ROI Inclusion ROI 0.1 0.1 * 2 0.06 0.08 /R * 0.08 2 R 0.04 0.06 Δ 0.06 0.02 0.04 0.04 0 0.02 0.02 0 0 1 2 3 4 5 6 7 8 0 0 1 Field2 3Strength4 5(T) 6 7 8 0 1 2 3 4 5 6 7Field 8Strength (T) Field Strength (T) Field dependence of fMRI responses pcorr < 0.05 for motor task 0.14 7 T 3 T 0.12 1.5 T Motor task (8 s ON; 20 s off; 5 0.1 cycles) 0.08 Same 6 subjects scanned at 0.06 S/S Δ 0.04 1.5, 3 & 7 T 0.02 Data co-registered across fields 0 and echo times. 0 20 40 60 80 100 TE (ms) W. van der Zwaag, S. Francis, K. E. Head, A. Peters, P. Gowland, P. Morris and R. Bowtell, Neuroimage 47, 1425-1434 (2009) High resolution somatosensory mapping at 7T ventral 3 2 4 5 1 right dorsal little anterior 1-thumb 2-index 3-middle 4-ring 5- posterior Relating structure to function in the visual cortex at 7T lateral fMRI medial Rotating wedge 1.5 mm isotropic resolution Structural posterior anterior structural Stria of Gennari seen as a dark band V1 functional Resolution:0.35x0.35x1.5mm3 Resting state networks Correlation coefficients for sensorimotor and default mode resting state networks J.R. Hale, M.J. Brookes, E.L. Hall, J.M. Zummer, C.M. Stevenson, S.T. Francis and P.G. Morris, Magn. Reson. Mater. Phy. 23, 339-349 (2010) Default mode network J.R. Hale, M.J. Brookes, E.L. Hall, J.M. Zummer, C.M. Stevenson, S.T. Francis and P.G. Morris, Magn. Reson. Mater. Phy. 23, 339-349 (2010) Sternberg Working Memory Task Paradigm: Two visual stimuli presented in quick succession Following a maintenance period of 8s, a third “probe” stimulus presented Subject responds if the the probe is the same as either of the two initial stimuli Visual Visual Probe Stimulus 1 Stimulus 2 Stimulus M a i n t e n a n c e P e r i o d Working Memory (Sternberg) Paradigm S. Clare, M. Humberstone, J.L. Hykin, L.D. Blumhardt, R. Bowtell and P.G. Morris, Magn Reson Med 42, 1117-1122 (1999) Challenges of pharmacological MRI • Direct affect (BOLD response) of agent – DifferenCaon between direct and acCvity mediated effects on haemodynamic response – Pharmacodynamics • Modulatory effect of agent – Pharmacodynamics Rat Model of Persistent Nociception Intraplantar injection of formalin into rat hindpaw Ascending and descending pain pathways Formalin evoked increase in BOLD response hl fl Hindlimb area of Somatosensory cortex vl vpm ThalamusThalamus vpl P<0.001 a Amygdala P<0.01 PAGPAG P<0.05 P.G. Morris, J. Psychopharm. 13 (4), 330-336 (1999) Effects of morphine injection 2 2 Periaqueductal Thalamus 1.5 1.5 gray 1 morphine 1 saline morphine saline 0.5 0.5 0 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 Time in minutes -0.5 % change in signal intensity -0.5 % change in signal intensity signal in change % Time in minutes 2 Cingulate cortex An acute high dose of 1.5 morphine (5mg/kg, IP cannula) evoked significant 1 morphine saline increases (p<0.002) in 0.5 BOLD response in the PAG, 0 thalamus and cingulate 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 cortex -0.5 % change in signal intensity intensity signal in change % Time in minutes MEG at the SPMMRC MEG beamformer w3 m3 w 2 Σ w275 m2 m275 w1 m1 V = w m q Σi=1..275 qi i virtual electrode output w m VE = 1 1+ w2m 2+ w3m 3 + Retinotopic mapping using MEG Stimulus was a rotating wedge containing a 10Hz flashing checkerboard. Wedge rotated through 360 degrees smoothly once every 25 seconds. Functional images created using adaptive beamformer using short covariance windows Functional images show the location of the 10Hz driven neuromagnetic response Response is mapped retinotopically onto the occipital cortex M. J. Brookes, J. M. Zumer, C. M. Stevenson, J. R. Hale, G. R. Barnes, J. Vrba, and P. G. Morris, Neuroimage 49(1), 525-538 (2010) MEG responses • Evoked response • Gamma band ERS • Beta band ERD and ERS Hilbert Transform of VE timecourse from peak of gamma 60-80Hz Subj2 3 2.5 2 1.5 Source Strength Q(nAm) Strength Source 1 0.5 0 500 1000 1500 2000 2500 3000 3500 4000 4500 5000 Samples Multimodal imaging: fMRI / MEG fMRI MEG β-band ERS (15-30Hz) 7T BOLD Ŧ>1.2 T>6 β-band ERD (15-30Hz) Ŧ>1.2 3T BOLD VEP Ŧ>5 T>5.5 γ-band ERS (60-80Hz) M.J. Brookes, A.M. Gibson, S.D. Hall, P.L. Furlong, G.R. Ŧ>4 Barnes, A. Hillebrand, K.D. Singh, I.E. Holliday, S.T. Francis, P.G. Morris, Neuroimage 26 (1), 302-308 (2005) MEG Contrast Response Curves 1.1 1.1 1 1 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 Normalised VEF Response Normalised 0.1 0.1 Gamma Response Normalised 0 0 -0.1 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 A Michelson Contrast B Michelson Contrast 0.2 1 0.1 0.9 0 0.8 -0.1 0.7 -0.2 0.6 -0.3 0.5 -0.4 0.4 -0.5 0.3 -0.6 0.2 -0.7 0.1 -0.8 0 Normalised Beta ERS Response Beta Normalised Normalised Beta ERD Response Beta Normalised -0.9 -0.1 -1 -0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 -0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 C Michelson Contrast D Michelson Contrast Correlation of fMRI BOLD with neural oscillations J.M. Zumer, M.J. Brookes, C.M. Stevenson, S.T. Francis and P. G. Morris, Neuroimage 49(2) 1479-1489 (2010) Working memory N-back and Sternberg paradigms N-BACK TARGETS A… H S S G V D P… X S S D V K D… H Y R D V D 1-BACK 0-BACK 2-BACK RELAX 0 32 64 96 126 Time (s) STERNBERG TARGET A D Y C Y M S P C LETTER MAINTENANCE RELAX RELAX RELAX PRESENTATION PROBE 2, 5 or 8 letters: 1 8s 8s Time (s) 1.4s letter presented 2s every 1.4s Number of Subjects 8 Positive Change Positive Change Negative Change Negative Change 7 Number of Subjects 8 Positive Change Positive Change Negative Change Negative Change 5 Theta (4-8 Hz) activity during N-back (upper) and Sternberg (lower) paradigms. Group effect. Number of Subjects 8 Positive Change Positive Change Negative Change 7 Number of Subjects 8 Positive Change Positive Change Negative Change 7 Gamma (20-40 Hz) activity during N-back (upper) and Sternberg (lower) paradigms Group effect Spectral changes in oscillatory power in medial frontal lobe: N-back Spectral changes in oscillatory power in medial frontal lobe: Sternberg M.J. Brookes, J.R. Wood, C.M. Stevenson, J.M. Zumer, T.P. White, P.F. Liddle and P.G. Morris, Neuroimage 55, 1804-1815 (2011) ICA analysis of resting state data M.Brookes, M. Woolrich, H. Luckoo, D. Price, J.R. Hale, M.C. Stephenson, G.R. Barnes, S.M. Smith and P.G. Morris, PNAS 108 (40), 16783-16788 (2011) ICA analysis of resting state data M.Brookes, M. Woolrich, H. Luckoo, D. Price, J.R. Hale, M.C. Stephenson, G.R. Barnes, S.M. Smith and P.G. Morris, PNAS 108 (40), 16783-16788 (2011) Resting state networks: MEG Brookes et al. PNAS 108 (40): 16783-16788 (2011) Resting state brain networks observable using both fMRI and MEG in the “resting state” Shows that the haemodynamic networks in fMRI have an electrophysiological basis MEG also shows that neural oscillatory processes underlies haemodynamic connectivity Agrees with invasive measurements made in patients Networks associated with working memory tasks A: Visual, B: Fronto-Parietal, C: L/R Insula, D L/R TPJ, E: R Motor, F: L Motor, G Lateral Visual, H: Medial Parietal Sternberg Working Memory Task Paradigm: Two visual stimuli presented in quick succession Following a maintenance period of 8s, a third “probe” stimulus presented Subject responds if the the probe is the same as either of the two initial stimuli Visual Visual Probe Stimulus 1 Stimulus 2 Stimulus M a i n t e n a n c e P e r i o d Sternberg Working Memory Task Primary visual areas Medial Parietal cortex Lateral visual areas Bilateral TPJ Bilateral Insula network Right Motor Cortex Fronto-parietal network Left Motor Cortex Time frequency plots for 8 networks associated with Sternberg paradigm Brain Neurotransmission Pathways of Glu/Gln and GABA/Glu/Gln Cycling" Glutamatergic neuron Astrocyte GABAergic neuron Glu GAD67 TCA GABAc TCA Gln Gln Gln Cycle GAD65 Cycle TCA Cycle GABA Glu Glu GABA Na+ Na+ Advantages of high field for MRS •! Increased SNR (~ B0) –! improved spa0al resolu0on –! shorter scan 0mes •! Increased spectral resolu0on •! Simpler spin coupling paVerns –! weak rather than strong coupling 1H MRS Repeatability: %CVs Click to edit Master title style •! Click to edit Master text styles •! Second level NAA Glu •! ThirdGln levelmI GABA Cr Cho 7T sh 3 (2) 4(2) 10(6) 9(3) 10(6) 3(2) 5(4) 3T sh 5(3) 8(6) •! Fourth29(11) 8(4) level 21(14) 10(4) 16(16) 7T long 6(6) 10(6) 29(19) 19(10) 16(8) 7(6) 8(6) 3T long 6(6) 16(9) •! 32(30)Fifth 22(10)level 36(25) 22(13) 8(7) Values are mean (± SD) M.