Trends in Neurosciences
ReviewfMRI and its interpretations: an illustration on directional selectivity in area V5/MT
Introduction
Functional magnetic resonance imaging (fMRI) produces reliable and reproducible results in various fields of research. Typically, fMRI signals are thought to represent changes in the activity of the neuronal populations responsible for the task at hand. This assumption has historical rather than scientific origins, as various degrees of stimulus or task selectivity have long been demonstrated with intracortical recordings from isolated single neurons in experimental animals. fMRI activation is thus presumed to reflect an increase in the spiking rate of those specialized neurons underlying the subject's behavior. Yet, research using diverse methodologies has also demonstrated that hemodynamic responses are more sensitive to integrative dendro-somatic processes than the spiking of a few stimulus- or task-selective cortical projection neurons. In other words, strong evidence exists that although fMRI undoubtedly provides valuable information regarding regional changes of neural activity, it does so by stressing neural processes that might be different from those reported in invasive animal experiments.
In this review, we examine to what extent common fMRI data reflect the functional properties of neurons by considering a special example: the neuroimaging data on neuronal directional selectivity, initially reported in electrophysiological studies, in cortical area V5 (also known as MT). The aim is to show how imaging data can or should be interpreted. Can fMRI be seen to provide a pooled (yet whole-brain) version of signals otherwise provided by electrophysiology? Can clever experimental paradigms allow us to infer neuronal spiking properties from blood-oxygen-level-dependent (BOLD) signals? Can they circumvent the limits given by its spatial resolution? Given the exponential growth of noninvasive neuroimaging experiments in human, and given their ethical advantages over electrophysiology, these questions are central to basic science and to policymaking. With this aim, this review attempts to combine knowledge from neurophysiology, applied fMRI and neurovascular coupling (NVC) to address the above questions. We use concrete examples from functional studies and focus mainly on the cortical region of V5+/MT+, as it has been one of the most intensely studied regions both in physiology and imaging. We hope that any conclusions reached will have more general implications.
Section snippets
Functional properties of area V5
Many years of electrophysiological research have convincingly demonstrated that area V5 of the monkey brain contains an abundance of neurons selective for the direction of movement of the visual stimulus (e.g. see reviews in Refs 1, 2, 3, 4). In addition, single-cell recordings and microstimulation experiments also suggest that V5 neurons play a direct role in the perception of motion direction and speed, because spontaneous or electrically induced fluctuations of activity correlate with
Neurophysiology of BOLD signal
Even though fMRI measures neural activity indirectly and with a (standard) resolution in the range of millimeters across the whole brain, the mapping of certain features such as visual contrast, color, motion, faces and language have produced highly reliable results under various experimental conditions that coincide with those obtained in clinical as well as in electrophysiological studies 15, 17, 18, 19, 20, 21, 22. The temporal resolution of BOLD signal with time constants in the range of
Neurophysiological signals
The signal measured by microelectrodes reports both dendro-somatic integrative and spiking activity. The former is typically captured by the so-called local field potentials (LFP), which report population synaptic potentials and interneuronal interactions, that is, local cortical processing [30]. LFP signals are spatially localized and stimulus selective 31, 32, 33.
Spikes, generally speaking, are the well-known electrical discharges of neurons. Without them, nothing would be happening in
Neurovascular coupling
Because there are plenty of excellent reviews on NVC, we keep this section brief to merely aid as a reminder. BOLD signal reflects cerebral blood flow (CBF) and tissue oxygenation, which in turn change in proportion to the regional energy consumption. The latter is dominated by perisynaptic events, including neurotransmitter recycling and restoration of ionic gradients of postsynaptic membranes 26, 30, 34. It is not spiking activity but this perisynaptic activity that dominates the control of
Evidence on the basis of fMRI adaptation experiments
The prime tool used in fMRI to circumvent the problem of resolution has relied on neural adaptation 51, 52. Note that in psychophysics, adaptation is highly valuable, as it provides unambiguous indication of a neural interaction between distinct stimulus conditions. Electrophysiology studies adaptation in its own right, for example to examine neural mechanisms of spatial integration as discussed below [53]. fMRI, by contrast, has attempted to use adaptation (fMRI-A) as a means to infer and map
Complex motion: opponency and pattern integration
Another simple and compelling fMRI attempt to segregate sites containing DSN (e.g. V1) from those exhibiting DSN with motion opponency (e.g. V5; see above) was to expose human observers to unidirectionally drifting sinusoidal gratings, or to the sum of two superimposed gratings moving in opposite directions (counterphase gratings) 73, 74. The latter are perceived as stationary, contrast-inversing gratings, possibly as a result of the motion-opponency stage. In regions containing
Perception and attention
Physiological signals tend to be higher when stimuli are perceived as opposed to when they are not and, intriguingly, in some regions such as V5+, BOLD signal has appeared to reflect this more sensitively than electrophysiological measures 81, 82, 83. This phenomenon has been addressed most extensively using bistable percepts, such as in binocular rivalry, where the percept alternates spontaneously, despite constant physical stimulation.
Higher areas including V4, V5 and inferotemporal regions
Classifiers and high-resolution imaging
The key weakness in identifying direction-selective responses in V5+ is the mixed populations of neurons in V5+ within a single voxel. Adaptation methods failed to circumvent this problem as they rely on a spike-based interpretation of the signal, and additionally alter neural properties also in potentially nonselective downstream sites. However, the columnar organization of many cortical areas might allow for a direct identification of direction-selective responses (see Figure 3). To achieve
Other noninvasive evidence for DSN in V5
The question remains whether there is any conclusive evidence for directionally selective neurons in human V5+. In one study, direct electrical stimulation of the visual cortex of an epileptic patient was shown to selectively impair motion perception in a particular direction, and some patients with damage in that region report similar deficits [110]. Unfortunately, the poor spatial specificity of both approaches left it unclear whether the effects really originated from V5+, therefore still
Conclusion
Our primary question here was to what extent noninvasive methods such as fMRI can inform about neural properties that are below the method's resolving power. We specifically examined the evidence for directional selectivity in one of the best studied cortical regions in neuroscience, the motion-processing area V5 (MT). Whereas many functional properties have identified and established human V5 as a homologue of monkey V5/MT, most studies fail to convincingly demonstrate the directional
Acknowledgements
We thank Semir Zeki and Bruno Weber for insightful discussions and comments on the manuscript.
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