Which “neural activity” do you mean? fMRI, MEG, oscillations and neurotransmitters

Over the last 20 years, BOLD-FMRI has proved itself to be a powerful and versatile tool for the study of the neural substrate underpinning many of our cognitive and perceptual functions. However, exactly how it is coupled to the underlying neurophysiology, and how this coupling varies across the brain, across tasks and across individuals is still unclear. The story is further complicated by the fact that within the same cortical region, multiple evoked and induced oscillatory effects may be modulated during task execution, supporting different cognitive roles, and any or all of these may have metabolic demands that then drive the BOLD response. In this paper I shall concentrate on one experimental approach to shedding light on this problem i.e. the execution of the same experimental tasks using MEG and fMRI in order to reveal which electrophysiological responses best match the BOLD response spatially, temporally and functionally. The results demonstrate a rich and complex story that does not fit with a simplistic view of BOLD reflecting "neural activity" and suggests that we could consider the coupling between BOLD and the various parameters of neural function as an ill-posed inverse problem. Finally, I describe recent work linking individual variability in both cortical oscillations and the BOLD-fMRI response to variability in endogenous GABA concentration.

[1]  Barry Horwitz,et al.  Interpreting PET and fMRI measures of functional neural activity: the effects of synaptic inhibition on cortical activation in human imaging studies , 2001, Brain Research Bulletin.

[2]  G. Iannetti,et al.  BOLD functional MRI in disease and pharmacological studies: room for improvement? , 2007, Magnetic resonance imaging.

[3]  W. Singer,et al.  Hemodynamic Signals Correlate Tightly with Synchronized Gamma Oscillations , 2005, Science.

[4]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  Derek K. Jones,et al.  Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans , 2009, Proceedings of the National Academy of Sciences.

[6]  S. Muthukumaraswamy,et al.  Functional and structural correlates of the aging brain: Relating visual cortex (V1) gamma band responses to age‐related structural change , 2012, Human brain mapping.

[7]  Matthew J. Brookes,et al.  GLM-beamformer method demonstrates stationary field, alpha ERD and gamma ERS co-localisation with fMRI BOLD response in visual cortex , 2005, NeuroImage.

[8]  Morten L. Kringelbach,et al.  Visual word recognition: the first half second , 2004, NeuroImage.

[9]  T. Hafting,et al.  Frequency of gamma oscillations routes flow of information in the hippocampus , 2009, Nature.

[10]  Timothy P. L. Roberts,et al.  Relating MEG measured motor cortical oscillations to resting γ-Aminobutyric acid (GABA) concentration , 2011, NeuroImage.

[11]  J. Maunsell,et al.  Differences in Gamma Frequencies across Visual Cortex Restrict Their Possible Use in Computation , 2010, Neuron.

[12]  Adrian T. Lee,et al.  fMRI of human visual cortex , 1994, Nature.

[13]  J. Palva,et al.  New vistas for α-frequency band oscillations , 2007, Trends in Neurosciences.

[14]  Rodrigo F. Salazar,et al.  Responses to natural scenes in cat V1. , 2003, Journal of neurophysiology.

[15]  P. Boesiger,et al.  GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI , 2007, Nature Neuroscience.

[16]  Roberto Cabeza,et al.  Aging Gracefully: Compensatory Brain Activity in High-Performing Older Adults , 2002, NeuroImage.

[17]  R. Eckhorn,et al.  Perception-related modulations of local field potential power and coherence in primary visual cortex of awake monkey during binocular rivalry. , 2004, Cerebral cortex.

[18]  S. J. Swithenby,et al.  Semantic and phonological task-set priming and stimulus processing investigated using magnetoencephalography (MEG) , 2007, Neuropsychologia.

[19]  Silvia Mangia,et al.  Metabolic and Hemodynamic Events after Changes in Neuronal Activity: Current Hypotheses, Theoretical Predictions and in vivo NMR Experimental Findings , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[20]  Rosa Cao,et al.  The hemo-neural hypothesis: on the role of blood flow in information processing. , 2008, Journal of neurophysiology.

[21]  R. Edden,et al.  In vivo magnetic resonance spectroscopy of GABA: a methodological review. , 2012, Progress in nuclear magnetic resonance spectroscopy.

[22]  I. Fried,et al.  Coupling Between Neuronal Firing, Field Potentials, and fMRI in Human Auditory Cortex , 2005, Science.

[23]  J. Bullier,et al.  Cortical mapping of gamma oscillations in areas V1 and V4 of the macaque monkey , 2001, Visual Neuroscience.

[24]  K. Fujii,et al.  Visualization for the analysis of fluid motion , 2005, J. Vis..

[25]  G. Barnes,et al.  Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography , 2009, Human brain mapping.

[26]  Pascal Fries,et al.  The Model- and the Data-Gamma , 2009, Neuron.

[27]  M. Garwood,et al.  Simultaneous in vivo spectral editing and water suppression , 1998, NMR in biomedicine.

[28]  Fiona E. N. LeBeau,et al.  Multiple origins of the cortical gamma rhythm , 2011, Developmental neurobiology.

[29]  E. Halgren,et al.  Dynamic Statistical Parametric Mapping Combining fMRI and MEG for High-Resolution Imaging of Cortical Activity , 2000, Neuron.

[30]  Adrian L. Williams,et al.  Task-Related Changes in Cortical Synchronization Are Spatially Coincident with the Hemodynamic Response , 2002, NeuroImage.

[31]  Matthew J. Brookes,et al.  Relating BOLD fMRI and neural oscillations through convolution and optimal linear weighting , 2010, NeuroImage.

[32]  J. Maunsell,et al.  Different Origins of Gamma Rhythm and High-Gamma Activity in Macaque Visual Cortex , 2011, PLoS biology.

[33]  C. Koch,et al.  Invariant visual representation by single neurons in the human brain , 2005, Nature.

[34]  H. Berger On the electroencephalogram of man. , 1969, Electroencephalography and clinical neurophysiology.

[35]  W. Singer,et al.  Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[36]  D. Attwell,et al.  The neural basis of functional brain imaging signals , 2002, Trends in Neurosciences.

[37]  S. Lowen,et al.  Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation , 2011, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[38]  Xiao-Jing Wang,et al.  What determines the frequency of fast network oscillations with irregular neural discharges? I. Synaptic dynamics and excitation-inhibition balance. , 2003, Journal of neurophysiology.

[39]  Stephen D. Hall,et al.  GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke – A case report , 2010, Clinical Neurophysiology.

[40]  O. Bertrand,et al.  Cross-Frequency Coupling in Parieto-Frontal Oscillatory Networks During Motor Imagery Revealed by Magnetoencephalography , 2009, Front. Neurosci..

[41]  Gareth R. Barnes,et al.  Group imaging of task-related changes in cortical synchronisation using nonparametric permutation testing , 2003, NeuroImage.

[42]  D. Johnston,et al.  Negative Blood Oxygen Level Dependence in the Rat:A Model for Investigating the Role of Suppression in Neurovascular Coupling , 2010, The Journal of Neuroscience.

[43]  J. Palva,et al.  New vistas for alpha-frequency band oscillations. , 2007, Trends in neurosciences.

[44]  K. D. Singh,et al.  Spectral properties of induced and evoked gamma oscillations in human early visual cortex to moving and stationary stimuli. , 2009, Journal of neurophysiology.

[45]  Krish D. Singh,et al.  Orientation Discrimination Performance Is Predicted by GABA Concentration and Gamma Oscillation Frequency in Human Primary Visual Cortex , 2009, The Journal of Neuroscience.

[46]  Arjan Hillebrand,et al.  The temporal sequence of evoked and induced cortical responses to implied‐motion processing in human motion area V5/MT+ , 2007, The European journal of neuroscience.

[47]  F. L. D. Silva,et al.  Event-related EEG/MEG synchronization and desynchronization: basic principles , 1999, Clinical Neurophysiology.

[48]  R. Shapley,et al.  LFP power spectra in V1 cortex: the graded effect of stimulus contrast. , 2005, Journal of neurophysiology.

[49]  Stephen J. Anderson,et al.  The spatial distribution and temporal dynamics of brain regions activated during the perception of object and non-object patterns , 2007, NeuroImage.

[50]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[51]  Krish D. Singh,et al.  Induced visual illusions and gamma oscillations in human primary visual cortex , 2004, The European journal of neuroscience.

[52]  Krish D. Singh,et al.  Cortical oscillatory changes in human middle temporal cortex underlying smooth pursuit eye movements , 2013, Human brain mapping.

[53]  Karl J. Friston,et al.  An In Vivo Assay of Synaptic Function Mediating Human Cognition , 2011, Current Biology.

[54]  Gareth R. Barnes,et al.  The missing link: analogous human and primate cortical gamma oscillations , 2005, NeuroImage.

[55]  Derek K. Jones,et al.  Visual gamma oscillations and evoked responses: Variability, repeatability and structural MRI correlates , 2010, NeuroImage.

[56]  Suresh D Muthukumaraswamy,et al.  Functional properties of human primary motor cortex gamma oscillations. , 2010, Journal of neurophysiology.

[57]  Philippe Kahane,et al.  Task‐related gamma‐band dynamics from an intracerebral perspective: Review and implications for surface EEG and MEG , 2009, Human brain mapping.

[58]  J. Vrba,et al.  Signal processing in magnetoencephalography. , 2001, Methods.

[59]  W. Singer,et al.  Synchronization of Visual Responses between the Cortex, Lateral Geniculate Nucleus, and Retina in the Anesthetized Cat , 1998, The Journal of Neuroscience.

[60]  F. Tong,et al.  Decoding the visual and subjective contents of the human brain , 2005, Nature Neuroscience.

[61]  D. Hubel,et al.  Receptive fields, binocular interaction and functional architecture in the cat's visual cortex , 1962, The Journal of physiology.

[62]  F. Carver,et al.  Complex relationship between BOLD signal and synchronization/desynchronization of human brain MEG oscillations , 2007, Human brain mapping.

[63]  N. Logothetis What we can do and what we cannot do with fMRI , 2008, Nature.

[64]  W Singer,et al.  Visual feature integration and the temporal correlation hypothesis. , 1995, Annual review of neuroscience.

[65]  Andreas A. Ioannides,et al.  Consistent and precise localization of brain activity in human primary visual cortex by MEG and fMRI , 2003, NeuroImage.

[66]  David J. McGonigle,et al.  Test–retest reliability in fMRI: Or how I learned to stop worrying and love the variability , 2012, NeuroImage.

[67]  R G Shulman,et al.  Interpreting functional imaging studies in terms of neurotransmitter cycling. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[68]  H. Johansen-Berg,et al.  The Role of GABA in Human Motor Learning , 2011, Current Biology.

[69]  Arjan Hillebrand,et al.  The temporal frequency tuning of human visual cortex investigated using synthetic aperture magnetometry , 2004, NeuroImage.

[70]  A. Engel,et al.  Cortical Network Dynamics of Perceptual Decision-Making in the Human Brain , 2011, Frontiers in Human Neuroscience.

[71]  Ingo Fründ,et al.  Inter- and Intra-Individual Covariations of Hemodynamic and Oscillatory Gamma Responses in the Human Cortex , 2009, Front. Hum. Neurosci..

[72]  Jong H. Yoon,et al.  GABA Concentration Is Reduced in Visual Cortex in Schizophrenia and Correlates with Orientation-Specific Surround Suppression , 2010, The Journal of Neuroscience.

[73]  Petroc Sumner,et al.  Individual Differences in Subconscious Motor Control Predicted by GABA Concentration in SMA , 2010, Current Biology.

[74]  Peter B Barker,et al.  Spatial effects in the detection of γ‐aminobutyric acid: Improved sensitivity at high fields using inner volume saturation , 2007, Magnetic resonance in medicine.

[75]  Robert Oostenveld,et al.  Localizing human visual gamma-band activity in frequency, time and space , 2006, NeuroImage.

[76]  Krish D. Singh,et al.  Functional decoupling of BOLD and gamma‐band amplitudes in human primary visual cortex , 2009, Human brain mapping.

[77]  Peter Jezzard,et al.  Baseline GABA concentration and fMRI response , 2010, NeuroImage.

[78]  D. Lewis,et al.  Alterations of Cortical GABA Neurons and Network Oscillations in Schizophrenia , 2010, Current psychiatry reports.

[79]  R J Ilmoniemi,et al.  Spatiotemporal activity of a cortical network for processing visual motion revealed by MEG and fMRI. , 1999, Journal of neurophysiology.

[80]  Krish D. Singh,et al.  A new approach to neuroimaging with magnetoencephalography , 2005, Human brain mapping.

[81]  R. Hess,et al.  Selectivity of human retinotopic visual cortex to S‐cone‐opponent, L/M‐cone‐opponent and achromatic stimulation , 2007, The European journal of neuroscience.

[82]  G. Barnes,et al.  Induced Gamma activity in primary visual cortex is related to luminance and not color contrast: An MEG study. , 2008, Journal of vision.

[83]  N. Logothetis,et al.  Local field potential reflects perceptual suppression in monkey visual cortex , 2006, Proceedings of the National Academy of Sciences.

[84]  J W Belliveau,et al.  Borders of multiple visual areas in humans revealed by functional magnetic resonance imaging. , 1995, Science.

[85]  A. Lawrence,et al.  Dorsolateral Prefrontal-Aminobutyric Acid in Men Predicts Individual Differences in Rash Impulsivity , 2011 .

[86]  Krish D. Singh,et al.  Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in primary visual cortex , 2008, NeuroImage.

[87]  P. Morris,et al.  β‐Band correlates of the fMRI BOLD response , 2011, Human brain mapping.

[88]  A. Thiele,et al.  Comparison of spatial integration and surround suppression characteristics in spiking activity and the local field potential in macaque V1 , 2008, The European journal of neuroscience.

[89]  P. Fries A mechanism for cognitive dynamics: neuronal communication through neuronal coherence , 2005, Trends in Cognitive Sciences.

[90]  Essa Yacoub,et al.  High-field fMRI unveils orientation columns in humans , 2008, Proceedings of the National Academy of Sciences.

[91]  Afonso C. Silva,et al.  Elevated endogenous GABA level correlates with decreased fMRI signals in the rat brain during acute inhibition of GABA transaminase , 2005, Journal of neuroscience research.

[92]  A. Bompas,et al.  More GABA, less distraction: a neurochemical predictor of motor decision speed , 2010, Nature Neuroscience.

[93]  S. Muthukumaraswamy,et al.  Individual variability in the shape and amplitude of the BOLD‐HRF correlates with endogenous GABAergic inhibition , 2012, Human brain mapping.

[94]  Ulf Knoblich,et al.  What do We Gain from Gamma? Local Dynamic Gain Modulation Drives Enhanced Efficacy and Efficiency of Signal Transmission , 2010, Front. Hum. Neurosci..

[95]  W. Medendorp,et al.  Modulations in oscillatory activity with amplitude asymmetry can produce cognitively relevant event-related responses , 2009, Proceedings of the National Academy of Sciences.

[96]  I. Toni,et al.  Oscillations , 2018, Physics to a Degree.

[97]  M. Siegel,et al.  A framework for local cortical oscillation patterns , 2011, Trends in Cognitive Sciences.

[98]  O. Jensen,et al.  Cross-frequency coupling between neuronal oscillations , 2007, Trends in Cognitive Sciences.

[99]  W. Singer,et al.  The gamma cycle , 2007, Trends in Neurosciences.

[100]  D. Cheyne,et al.  Localization of human somatosensory cortex using spatially filtered magnetoencephalography , 2003, Neuroscience Letters.