local action for global vision

J Physiol 589.14 (2011) pp 3419–3420 3419

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Local action for global vision

Maxim VolgushevDepartment of Psychology, University ofConnecticut, Storrs, CT 06269, USA

Email: maxim.volgushev@uconn.edu

Active brain cells use oxygen, butexactly how neurone activity drives brainmetabolism is poorly understood. A paperby Li & Freeman (2011) in a recent issue ofThe Journal of Physiology sheds light on thisimportant question, by demonstrating howindistinguishable patterns of local neuralresponses can be accompanied by distinctpatterns of brain oxygen consumption.They cleverly exploit the topographicorganisation of sensory cortices, using visualstimuli to manipulate the area of activatedcortex, and show that global corticalactivation can influence local measurementsof neural and metabolic activity. The resultsare important for understanding the basisof non-invasive measures of brain function.

The most common brain imagingtechniques are optical imaging ofintrinsic signals and functional magneticresonance imaging (fMRI). These methodsmeasure changes of the blood oxygenlevel-dependent (BOLD) signal. TheBOLD signal is of special importance inbrain science, because it can be measurednon-invasively in humans using fMRI. Putsimply, increased neuronal activity increasesenergy consumption, producing a decreasein tissue oxygen level (measured as the‘initial dip’ in the BOLD signal), followeda few seconds later by a reactive increase

Figure 1. Spatial relation between region of primary visual cortex activated by thestimuli and regions contributing to the recorded electrophysiological (MUA and LFP)and oxygen level (BOLD) signals

of blood and oxygen supply (the ‘positivepeak’). Herein, however, lies the problemof using BOLD signals to understand brainfunction: BOLD signals have slow dynamicsand coarse spatial scale. The BOLD signalbegins long after stimulus-evoked neuronalresponses, when cognitive processes suchas stimulus detection and recognition mayhave already been accomplished. Spatially,the initial dip probably integrates changesof tissue oxygen level over ∼0.2 mm2, andthe positive peak integrates over ∼2 mm2

(Thompson et al. 2005; Viswanathan& Freeman, 2007), encompassing manythousands of cortical neurones. Thus,neural signals and BOLD signals providecomplementary, different-scale views onhow the brain operates.

Changes of the BOLD signal are known tobe related to changes of neuronal activity,but the details of this relationship arecontroversial (reviewed in Logothetis 2008;Ekstrom, 2009). A key question remains:can similar changes of neuron activity beaccompanied by distinct BOLD signals? Thepaper by Li and Freeman gives a positiveanswer to this question.

The authors recorded from thebest-understood sensory cortex: theprimary visual cortex of cats. Theycombined recordings of neuronalmulti-unit activity (MUA) and localfield potential (LFP) with simultaneous,co-localized measurements of tissueoxygen level. Control neurone responsesand BOLD signals were first evokedwith patterned visual stimuli: patchesof optimally oriented moving gratings.Next, two different stimuli which suppressneuronal responses were tested. In the

first protocol (‘surround suppression’),neuronal responses are suppressed byincreasing the stimulus diameter. In thesecond (‘cross-orientation’), neuronalresponses are suppressed by superimposingan orthogonal grating on the optimallyoriented grating. Although neuronalresponses decreased in both cases, theBOLD signals were affected in a strikinglydifferent way. Surround suppressionproduced an increase of the initial dip, butno change of the positive peak of the BOLDsignal. In contrast, the cross-orientationprotocol yielded a decrease of the initial dipbut an increase of the positive peak.

How can we reconcile this apparent contra-diction, where one level of neuronal activityis accompanied by two distinct patterns ofbrain metabolism changes?

Consider what happens when stimulusdiameter is increased from 4 deg to 20 deg inthe surround suppression test. The strengthof thalamic input from the lateral geniculatenucleus (LGN) to the local recording site inthe cortex decreases only slightly becauseLGN neurones are barely sensitive to sizechange for stimuli over 2 deg diameter(Stone et al. 1979; Ozeki et al. 2009).More importantly, the large stimulus willactivate about 60–70% of the cat’s primaryvisual cortex (Tusa et al. 1978), includinglong-range projections to the recording sitefrom regions up to several millimetres away(Kisvarday et al. 1997). Activity around therecording electrode will be diminished asglobal and local inhibitory circuits workto stabilize the cortical network (Ozekiet al. 2009). A magnified BOLD initial dipcould result from increased local activityof the inhibitory neurones (as the authorssuggest), or as part of a more generalincrease of oxygen consumption over a verylarge (hundreds of mm2) activated corticalarea (Fig. 1). The BOLD positive peak doesnot increase with stimulus size, perhapsin part because the effect of local vaso-dilatation is shunted by the simultaneousvasodilatation over large regions of visualcortex.

In Li and Freeman’s second protocol ofcross-orientation suppression, the neuro-nal activity is modified in a very differentway. Responses of LGN neurons will beenhanced by addition of an orthogonal(‘mask’) grating (Freeman et al. 2002; Priebe& Ferster, 2006). However, the plaid-likespatial pattern of LGN inputs is sub-optimal

C© 2011 The Author. Journal compilation C© 2011 The Physiological Society DOI: 10.1113/jphysiol.2011.212670

3420 Perspectives J Physiol 589.14

for activation of orientation-sensitivecortical neurons at the recording site andtheir activity will be reduced (Priebe &Ferster, 2006), thus leading to the reductionof the initial dip. The overlapping maskstimulus will also activate cortical neuronsthat prefer the orientation of the mask. Thespatial grain of the cortical orientation mapmeans that these neurons would lie outsidethe sensitivity area of electrophysiologicalrecording, and outside the area contributingto the BOLD initial dip. But these neuroneswould lie within a broader area contributingto the vasodilation response, and theiractivity could explain why the BOLDpositive peak is increased.

The results reported by Li and Freemanprovide excellent illustration of twoimportant points. First, they clearly

demonstrate the complexity of relationsbetween neuronal activity and BOLDsignals. Changes of neuronal activitymay arise from activation of differentcircuits and be mediated via differentmechanisms. Although producing thesame final measured level of neuronalactivity, the difference in underlying circuitsmay be reflected by the BOLD signals.Second, the observations show why it isessential to consider large-scale patternsof neuronal activation for understandinglocally measured processes. This illustrativeexample shows the power of combinedelectrophysiological and brain imagingmethods which provide complementary,fine-grain and large-scale perspectives onneuronal activity, and most importantlyhelp to understand how they are related.

References

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Freeman TCB, Durand S, Kiper DC & CarandiniM (2002). Neuron 35, 759–771.

Kisvarday ZF, Toth E, Rausch M & Eysel UT(1997). Cerebral Cortex 7, 605–618.

Li B & Freeman RD (2011). J Physiol 589,3175–3190.

Logothetis N (2008). Nature 453, 869–878.Ozeki H, Finn IM, Schaffer ES, Miller KD &

Ferster D (2009). Neuron 62, 578–592.Priebe NJ & Ferster D (2006). Nat Neurosci 9,

552–561.Stone J, Dreher B & Leventhal A (1979). Brain

Res Reviews 1, 345–394.Thompson JK, Peterson MR & Freeman RD

(2005). J Neurosci 28, 9046–9058.Tusa RJ, Palomer RA & Rosenquist AC (1978).

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C© 2011 The Author. Journal compilation C© 2011 The Physiological Society