Theta-Gamma Coding Meets Communication-through-Coherence: Neuronal Oscillatory Multiplexing Theories Reconciled
[['Neural systems continually process multiple information sources at a time , such as the various items in a visual scene , or the components of an episodic memory .', 'It is widely accepted that the activity of different groups of neurons ( assemblies or ensembles ) represents the distinct items , and a general problem faced by such systems is that of overlap in the neural representations .', 'In a system such as the hippocampus , where representation is apparently distributed across the network , ensembles must literally overlap .', 'In more spatially structured systems , such as the retinotopic early visual system , the overlap arises because cells at later levels of the processing hierarchy have large receptive fields , potentially encompassing multiple stimulus items .', 'This overlap creates an ambiguity in the signal , a potential confusion of the stimulus features or active neurons attributed to each of the different objects .', 'It has long been recognized that one solution to this ambiguity would be to separate the activity of the different neuronal ensembles in the temporal domain [1] , and that neuronal oscillations present a mechanism whereby this might be achieved [2 , 3] .', 'In recent years there has been growing interest in cross-frequency coupling and the computations made possible by the interaction of oscillations at different frequencies[4 , 5] .', 'At present , two major theories have been proposed , each requiring the interaction of a fast ( gamma , 30–80 Hz ) and a slow ( alpha , 8–14 Hz , or theta , 3–8 Hz ) oscillation , and each developed on the basis of experimental evidence within one system , but purporting to potentially describe a more general , fundamental computational mechanism in the brain .', 'In this study , our aim was to test whether each of these theories is physiologically plausible , by implementing them within a unique network model inspired by physiological data , and to gain additional insights into the theories by doing so .', 'The first of these theories ( Fig 1B ) was initially developed on the basis of observed activity patterns in the rodent hippocampus [6–8] , and termed the ‘theta/gamma discrete phase code’ .', 'The theory has subsequently been extended to include a role in sensory systems [9–11] in which case experimental evidence suggests that the theta oscillation might be replaced by a slightly faster alpha oscillation .', 'According to this theory , neurons participating in a given ensemble fire together within a single gamma cycle , with the inhibitory portion of the gamma cycle yielding a temporal separation before the activation of the next ensemble .', 'The slow oscillation ( theta in the hippocampus , alpha in the early visual system ) structures the order of activation of the ensembles , because as the oscillatory inhibition fades on each cycle , more strongly activated ensembles are systematically activated earlier [12 , 13] .', 'This ordering would reflect the natural ordering of items in a memory system , or the relative salience of items presented to a sensory system [9] .', 'Depending on the ratio between fast and slow oscillatory frequencies as well as the “duty cycle” of the slow oscillation [9] , between two and seven or more items can be multiplexed in this way .', 'We will refer to this theory , for its principal developers Lisman and Jensen , as LJ-multiplexing .', 'The second theory ( Fig 1C ) was developed on the basis of experimental evidence from the visual system [14–17] .', 'In this case , items are not separated on the discrete cycles of a common gamma oscillation .', 'Instead , the activity of each ensemble is modulated by its own localized gamma oscillation , and it is the phase difference between these distinct oscillations that enables the selection and unambiguous processing of one individual item .', 'Downstream neuronal regions selectively process one item at a time through the synchronization of their own local gamma oscillation to that of the item in question , referred to as ‘communication-through-coherence’ ( CTC ) .', 'That is , although item representations overlap temporally in the lower area , only a single representation is active at a time in the higher area .', 'As such , the system described supports a mechanism of selection or attention .', 'While the original CTC theory focussed on the role of gamma oscillations and the sustained selection of a single item [14] , it was subsequently extended to consider slow ( theta or alpha ) oscillations as well [16 , 17] .', 'In this case , the slow oscillation plays the important role of regularly breaking interareal synchrony , providing a system reset that enables , potentially , processing of different items over time .', 'We will refer to this theory ( to make clear the distinction from the original gamma-only CTC theory ) as F-multiplexing , for its principal developer Fries .', 'Both of these theories have been presented as potentially generalized mechanisms of processing in the brain , although here for simplicity we shall focus on their potential role in perceptual processing .', 'At first sight , the two theories appear incompatible , since one of them depends on the selection of a unique item ( F-multiplexing ) while the other maintains multiple items in near-simultaneity ( LJ-multiplexing ) .', 'Each theory has received support from experimental evidence in this context .', 'In particular , for F-multiplexing , recent electrophysiological results ( local field potential and single-unit recordings ) have demonstrated modulation of interareal gamma coherence by attention , and theta-frequency fluctuations in gamma coherence [18–20] , exactly as predicted by the theory .', 'For LJ-multiplexing , evidence at the neuronal/network level relates mostly to the hippocampal system [21–24] , although modulation of gamma activity by the phase of alpha activity has recently been demonstrated in the primary visual cortex [25] ( this latter finding is equally supportive of F- as of LJ-multiplexing ) .', 'On the other hand , certain behavioural-level results hint rather at LJ-multiplexing in visual processing .', 'For example , the time required for a difficult visual search task increases with the number of distracter items .', 'If interpreted as an indication of serial processing of individual items in turn ( although this remains a controversial field e . g . [26] ) , these studies typically suggest processing times ranging from 20 to 60 ms per item [27] , values consistent with LJ-multiplexing at one item per gamma cycle ( around 25 ms ) , rather than F-multiplexing at one item per theta cycle ( 100–200 ms ) .', 'In order to test the mechanistic bases of these two multiplexing theories under physiological constraints , we developed a network model processing discrete stimulus objects .', 'The network had no specific function other than to decompose and represent its visual input in as faithful a way as possible .', 'In particular , we measured the temporal overlap between output neural responses coding for the different input stimuli , since this overlap could be construed as a failure to segregate input objects ( e . g . , yielding illusory conjunctions between features from different objects ) .', 'Both LJ- and F-multiplexing modes have been proposed as candidate mechanisms to prevent such temporal overlap .', 'We found that both LJ- and F-multiplexing modes can readily be implemented by a physiologically inspired network of spiking units , with a lower area establishing the temporal structure of the multiplexed signal , and a higher area decoding it .', 'Secondly , the two operating modes are mechanistically much more closely related than might at first be apparent , and a single physiologically valid parameter shift ( increasing the amplitude of global inhibition in the lower area , equivalent to the inclusion of a longer-range gamma oscillation ) can drive a switch between operating modes .', 'This raises the intriguing possibility that these two different theories are actually both correct and co-exist in the brain .', 'In that case , they may serve to implement an exploratory mode ( LJ-multiplexing ) and a selective processing mode ( F-multiplexing ) , and the system could dynamically switch between them as required .'], ['The design of our model ( Fig', '2 ) was guided by several simple principles .', 'These are detailed below , but in essence , our aim was to construct a network model incorporating several simple recognised characteristics , to test whether , and under what conditions it could generate activity resembling the major multiplexing theories .', 'In short , we included all the ingredients that would seem necessary to implement a multiplexing coding strategy .', 'Even then , however , it could be that these separate ingredients are not sufficient , and that the network never actually produces a behaviour resembling either of the major multiplexing schemes proposed in the literature .', 'Or it could be that one of these two schemes always dominates the network behaviour , regardless of the parameter regime .', 'Instead , we found that both F- and LJ- multiplexing behaviours could indeed be produced by this network , and that the shift between these modes required only a single change in parameters .', 'Both the theories under study have been proposed as general computational mechanisms within the cortex , and so we did not set out to simulate a specific system in detail .', 'Nonetheless , we found it useful to be able to present ‘real’ stimuli rather than abstract levels of activation , to more easily understand , contextualize and visualize the results .', 'Thus , we chose to base our model loosely on the early visual system , with a lower area approximating primary visual cortex ( V1 ) , and projections to a very basic second area ( Fig 2A ) .', 'Specifically , the lower area comprised a retinotopic layer of 348160 excitatory units with simple-cell like receptive fields ( Fig 2A ) , with lateral excitatory interactions and local inhibitory feedback via a layer of inhibitory interneurons ( Fig 2B ) .', 'Global inhibitory feedback ( modelled as a single interneuron receiving input from and sending feedback to all excitatory cells in the lower layer ) was included with variable amplitude and was an important parameter in determining the operating state of the network .', 'The higher area was deliberately designed to be simplistic , allowing a clear investigation of the dynamics in the lower area , and how these might establish interesting temporal interactions with a target region .', 'In the first instance , the higher area comprised just 4 excitatory cells , with purely spatial selectivity , each neuron receiving input from one retinotopic quadrant of the lower area ( thus each neuron would respond to any stimulus in the corresponding quadrant; after establishing the basic operation of the system , in a second section , we test a more functionally interesting network with overlapping inputs to the higher area ) .', 'We presented stimuli comprising discrete objects confined to these spatial quadrants , so that in effect , each neuron in the higher area responded to just one object .', 'Note that the network need not be interpreted as simulating the entire visual field but rather a functional region defined , e . g . , by the range of overlap of receptive fields in the higher area: cells with non-overlapping receptive fields can behave independently , and no multiplexing process is required at that scale .', 'The global inhibition that we refer to in both lower and higher areas should be understood in this context , as global to the functional region but not necessarily global to the whole anatomically defined brain area ( e . g . V1 or V4 ) .', 'Temporal dynamics within the model are critical to its behaviour in the current context and so we chose to simulate a spiking neuron network with cellular and synaptic parameters drawn from the experimental literature ( see Methods ) .', 'Particular attention was paid to the membrane and synaptic time constants , and net conductance values during activity .', 'The stimuli used comprised images with a mid-gray background , and from 1 to 4 discrete objects , each constrained to a different spatial quadrant .', 'The kind of excitatory-inhibitory network that we have implemented will readily generate oscillatory activity via a Pyramidal-Interneuron Gamma ( PING ) mechanism [28 , 29] ( diagrammatic representation in Fig 2C ) .', 'Pyramidal cell activity activates the local inhibitory network ( orange stars in the diagram ) .', 'Inhibitory feedback from these cells ( orange background ) shuts down the pyramidal cell activity .', 'As this inhibition decays , the pyramidal cells begin to fire again in a synchronized manner ( in our network , this synchrony is enhanced by local lateral excitation , so that the early-firing cells within an ensemble increase the probability that other members will fire soon afterwards ) .', 'This burst of firing sets in motion the next cycle of excitation-inhibition .', 'With physiological membrane time constants and synaptic dynamics , this system naturally generates rhythmic activity in the gamma frequency range ( Fig 2C ) .', 'Furthermore , there is a growing understanding of the stimulus dependence of gamma generation in the visual system , such that , e . g . , gamma frequency increases as a function of stimulus contrast [30 , 31] .', 'Again , this behaviour arises automatically in a PING network , because more strongly driven pyramidal cells recover more quickly from inhibitory suppression , illustrated for our network in Fig 2C .', 'We were thus able to set the contrast levels used so as to drive gamma oscillations over a realistic frequency range .', 'Simultaneous presentation of several objects with different contrast levels thus resulted in the generation of localized gamma oscillations at different frequencies for each ensemble ( 51 Hz for a full contrast object vs . 43 Hz for contrast = 0 . 8; note that this describes the situation with no global inhibition included ) .', 'Regarding the slow oscillation , generation of the hippocampal theta oscillation is complex and at least partially driven by input from external structures [32] .', 'Similarly , the cortical alpha oscillation likely involves thalamocortical interactions rather than a mechanism purely intrinsic to the local cortical network [33] .', 'To preserve simplicity , we thus opted to implement the slow oscillation as an external input , a rhythmically modulated conductance directly applied to all pyramidal cells in the lower area ( in the results reported here , no slow oscillation was applied to the higher area ) .', 'An inhibitory conductance was used , again based on the available physiological data: hippocampal theta activity , at least at the soma , is thought to be inhibitory [34 , 35]; alpha activity in the cortex tends to increase with inattention and decrease with attention , and is again considered likely to be inhibitory [36] .', 'We set the amplitude of this oscillation such that , at its peak , it completely suppressed firing in the lower layer ( comparable to the modulation of single units in hippocampus , e . g . [37] ) .', 'We used a slow oscillation frequency of 9 Hz in the results shown here , intermediate between the theta and alpha frequency bands of interest .', 'At this point we began to introduce and explore the additional features required to address the cross-frequency multiplexing theories .', 'We carried out a series of simulations ( 5 repeats of 2 seconds of simulated activity for each condition ) , exploring a set of parameter spaces ( the amplitudes and decay time constants of synaptic connections between the various neuronal populations in the network ) .', 'The stimulus comprised a 128 x 128 pixel image ( mid-gray background ) , with an object in three of the four quadrants , specifically white rectangles ( 9 x 39 pixels ) , with a single-pixel wide black outline , with contrast levels 1 ( top left ) , 0 . 95 ( bottom right ) and 0 . 9 ( top right ) .', 'Note this simplifying limitation in the model , representing inputs with an unrealistically limited range of absolute contrast levels .', 'However , the visual system includes well studied mechanisms of adaptation and contrast normalization dependent on stimulus statistics ( e . g . [38] ) such that the kinds of responses described here would actually be possible over a much greater range of contrast values .', 'In presenting the results from these simulations , we use a pair of measures ( see Methods ) that characterise the functioning states of the multiplexing modes under study , and convert these to a colour scale:', '1 ) spike separation , the temporal separation of activity driven by the different stimulus objects ( green for poor spike separation , i . e . activity is synchronous between the different objects , an indication of failure to implement either theory ) , and', '2 ) selectivity for a single object ( F-multiplexing , red ) vs sequential activation of different objects ( LJ-multiplexing , blue ) .', 'Fig 3A presents the resulting network states for a pair of key parameters revealed by these simulations , the amplitude of global inhibition in the lower versus the higher area ( all other parameters fixed in this plot ) .', 'With low levels of global inhibition in both areas ( Fig 3A , green area ) , spike separation was poor , as is apparent in the phase histogram of higher area activity ( Fig 3B ) .', 'In other words , the model did not produce any interesting multiplexing behaviour .', 'With increased global inhibition in the higher area ( Fig 3A , upper left red area ) , the network entered an F-multiplexing state , with selective activation of a single higher level neuron ( responding to the highest-contrast stimulus object ) at gamma frequency ( Fig 3C ) .', 'Alternatively , with increased global inhibition in the lower area only ( Fig 3A , lower right blue area ) , the network entered an LJ-multiplexing state , with higher area firing alternating between the high- and mid-contrast stimuli ( Fig 3D ) .', 'With global inhibition in both areas , overall firing tended to be reduced as some gamma cycles were skipped , and so encoding in this parameter range may be considered less efficient .', 'Nonetheless , the network state tended towards LJ-multiplexing , with firing alternating between different stimulus objects ( Fig 3E ) .', 'To help to understand the resulting changes in activity in the lower and higher areas , and how these brought about the different activity states , Fig 4 shows the results of a simulation ( 100 repeats ) , along with a diagrammatic representation , in which the changes to global inhibition were made over the course of the simulation run ( parameters corresponding to Fig 3B , 3C and 3E ) .', 'We first set out a point-by-point summary of the key ideas emerging from this simulation , and then describe them in more detail below: The slow oscillation has two hypothesised roles in the F-multiplexing system:', '1 ) a regular breaking of gamma synchrony to potentially allow the processing of different items across slow cycles [16 , 17] , and', '2 ) a regular reset of activity , central to the selection mechanism , and important to avoid the different gamma oscillations cycling in and out of phase with each other ( because of their slight differences in frequency ) [18] .', 'In Fig 5 , we show the results of a set of simulations ( 100 repeats each ) that support these conjectures .', 'In the following , the ‘selected’ object always refers to the highest contrast stimulus .', 'The first simulation shows the higher area activity when the slow oscillation was excluded ( Fig 5A ) .', 'A blank screen was presented for the first 200 ms , at which point the stimulus was turned on .', "The activity of the 'selected' object was favoured for the first hundred ms , but after that , selectivity was compromised ( compare to the robust selectivity obtained when the slow oscillation was included , Fig 5C ) .", 'The proportions of spikes for each object over the whole time period are shown in the histogram at the right .', 'Looking at the cross-correlogram for the activity , it is apparent that spikes for one object were often closely followed ( second spike within 0 to 3 ms for 20 . 8% of spikes ) by spikes for another .', 'That is , spike separation was compromised , exactly as predicted because the lower area gamma oscillations drift in and out of phase over time ( indeed , this drift in phase difference is directly apparent in the wave of responses to the medium contrast object from about 300 to 600 ms ) .', 'The activity was even further compromised in the second simulation ( Fig 5B ) , where rather than a blank screen , random pixelated white noise was presented for the first 200 ms , so that neurons were in a variable state at stimulus onset .', "In that case , activity for the 'selected' object was scarcely favoured in the early period , and spike separation was even more compromised ( second spike within 0 to 3 ms for 25 . 3% of spikes ) .", 'In the third simulation ( Fig 5C ) , the slow oscillation was restored , and as well as the noisy pre-stimulus period as above , a random delay was introduced to the timing of stimulus onset ( equal probability from 150 to 250 ms ) .', 'This effectively randomized the phase of the slow oscillation at which the stimulus occurred .', 'In spite of this variability , very strong selectivity was established from the next slow oscillation cycle following stimulus onset , and maintained throughout the simulation period .', 'The fourth simulation ( Fig 5D ) was similar except that the amplitude of the slow oscillation was halved , with the effect that some cells in the lower area were never fully suppressed .', 'As a result , when slow oscillatory inhibition fell , the near synchronous bursts of activity for each object were disrupted ( because the most strongly driven cells were refractory , and not available to participate in the ensembles ) , and communication with the higher area was impaired .', 'Note the paradoxical effect , that decreased inhibition in the lower area led to decreased activity in the higher area .', 'In the fifth simulation ( Fig 5E ) , we tested the ability of the system to switch selected object .', 'The initial period was as described for the third simulation ( pixelated noise , and variable stimulus onset time ) , but in this case each of the three stimulus objects was presented at full contrast , and instead the input gain for each quadrant ( which we conceive as the implementation of a top-down selection mechanism ) was modified: initially , it was set to match the previously used contrast values ( 1 , 0 . 95 and 0 . 9 for the top left , bottom right and top right quadrants , respectively ) , but after a delay ( three and a half cycles of the slow oscillation ) , the values for the first two quadrants were switched ( mimicking , e . g . a change in top-down spatial attention ) .', 'The network readily followed this change in selection , representing the top left object up to the time of the gain change , and then switching to the bottom right object .', 'Note that , even though the saliency switch occurred mid-way through the active part of the slow cycle ( arguably the most challenging situation for the model ) , object selection was rather resistant to that interruption: representation of the previously selected object continued until the end of the cycle , with only a small amount of activity relating to the newly prioritised object leaking through .', 'As predicted theoretically , the switch to representation of the new object occurred on the following slow cycle ( following breaking of inter-area communication by the slow oscillation ) .', 'Beyond this , it is apparent that , in the brain , abrupt stimulus changes result in phase resetting of slow oscillatory activity [e . g . 40 , 41] , likely enabling a rapid switch of attention to the salient event .', 'In the simulations presented above ( Figs 3 and 4 ) , it is apparent that for the LJ-multiplexing style , only two out of three objects are represented , whereas in the original theory a sequence of up to seven or more objects , one per gamma cycle , could be repeated or updated on each slow cycle .', 'As Fig 4C makes clear , the main barrier to multiple items being represented in the network is that , following their activation in a given gamma cycle , lower area neurons recover during the following cycle , and are sufficiently ready to activate again in the cycle after .', 'Thus , rather than an ordered sequence of activations ( ABC ) , the network alternates between the two most strongly driven ensembles ( ABA… ) and the weaker ensembles never get a chance to fire .', 'One obvious solution is for cells to be suppressed for a longer period following their activation , either by intrinsic spike-induced conductances ( e . g . Ca-activated K currents , [42] ) or by longer-acting local feedback inhibition .', 'We tested this idea ( Fig 6A ) , using a simulation ( 100 repeats ) with identical parameters to Fig 3D , except that the synaptic decay time constant for local inhibition in the lower area was increased from 3 ms to 20 ms . In that case , the network readily cycled through the three presented objects on each cycle of the slow oscillation .', 'Note that the original formulation of the theta-gamma coding theory allowed for the representation of 7 or more items , consistent with ideas about verbal working memory , and the frequency ratio of gamma and theta oscillations in the hippocampus [6] , whereas the lower ratio of gamma to alpha frequencies has led to representation of only three or four items being proposed for the visual system [9 , 11] .', 'The exclusion of low-saliency ensembles from the multiplexing sequence is actually an explicit prediction of the LJ-multiplexing theory [9 , 11] .', 'Similar to F-multiplexing , we also tested whether LJ-multiplexing was dependent on complete suppression of activity during part of the slow oscillation cycle .', 'Fig 6B shows the results of simulations , similar to Fig 6A , except that the amplitude of the slow oscillation was halved .', 'Again , synchrony in the lower area was disrupted , and communication of activity to the higher area impaired .', 'Two specific points are worth noting:', 'i ) the ordered representation of items ( highest contrast first ) , characteristic of LJ-multiplexing is also disrupted , predictably given that the transform from excitatory drive to phase of firing is known to be dependent on complete suppression of firing for a brief period [13]; and', 'ii ) from the cross-correlogram of activity for the different items ( Fig 6Bii ) , items are not represented simultaneously , but rather at discrete gamma cycle intervals–that is , the mechanism of item segregation via global inhibition in the lower area is robust to the loss of structuring brought about by the reduction in slow oscillation amplitude .', 'One of the principal computational advantages offered by ‘communication-through-coherence’ is the ability to maintain separation of stimulus signals in the face of substantial convergence and generalization in the processing hierarchy [16] .', 'This can be seen as a partial solution to the infamous “binding” problem [43] .', 'The temporal separation of representations achieved by LJ-multiplexing is potentially useful for the same goal .', 'In order to determine whether the multiplexing modes described really do offer this computational utility , we tested a slightly modified version of the model , as follows .', 'The challenge in this case is to have cells in the higher area that are selective for specific conjunctions of stimulus features but that will not give rise to ‘illusory conjunctions’ , that is , be erroneously activated if the requisite features are present in the stimulus display but spread across multiple objects ( bearing in mind the growth in receptive field size along the processing hierarchy as part of the increasing generalization ) .', 'Starting from the orientation selectivity already intrinsic to the lower area , we added a second simple feature channel , that of colour selectivity .', 'Again , this is not intended to reflect the detail of an actual mechanism in visual processing ( it is clear that processing of colour and orientation are not truly separated in primary visual cortex , [44] ) but rather a conceptually clear implementation of this general class of computational problem ( i . e . , feature binding ) .', 'In detail , retinotopic layers of colour-selective cells ( non-orientation selective ) for red , green and blue were added to the lower network area , precisely in parallel with the existing orientation-selective layers , and likewise duplicated across spatial scales ( Fig 7A ) .', 'Connections to and from the local inhibitory network were exactly as for the earlier model , and did not differentiate between the orientation-selective and colour-selective layer ( that is , activity in e . g . the orientation-selective cells could lead to local inhibition of the colour-selective cells ) .', 'The higher area was more substantially modified .', 'Spatial selectivity was removed , such that all cells received input from the full spatial extent of the lower area .', 'Instead , cells were made selective for specific colour-orientation conjunctions ( e . g . vertical-red ) .', 'This selectivity was established simply through targeted connectivity from the lower to higher area ( e . g . , the vertical-red cell receiving input only from the vertical- and red-selective cells in the lower area ) , along with tuning of the synaptic strength such that activity in both input channels was required to drive the cells to threshold .', 'One cell for each orientation-colour pair was included in the higher area ( thus , a 4 x 3 grid of cells , see Fig 7A ) .', 'We challenged this network with a stimulus comprising two objects with different colour-orientation features ( e . g . vertical-red and horizontal-blue ) .', 'It was straightforward to demonstrate that in a pure feedforward excitatory version of the network ( all local and global inhibitory activity turned off ) such a stimulus could successfully drive the relevant conjunction-selective cells in the higher area ( vertical-red and horizontal-blue ) but would also yield illusory conjunctions , by erroneously driving two cells selective for conjunctions not actually present in individual stimulus objects: vertical-blue and horizontal-red .', 'Fig 7B presents the activity in the lower and higher areas for the three more elaborate network states presented above ( c . f . Figs 3 and 4 ) .', 'First , we considered the default activity state ( c . f . Fig 4A; slow oscillation included , localized gamma activity generated intrinsically through a PING mechanism in the lower area ) .', 'Note that we presented the vertical-red object at higher contrast than the horizontal-blue ( 1 vs 0 . 95 ) , and so there was some degree of temporal separation between the bursts of synchronized activity in the lower area corresponding to each of the objects ( as above , the more strongly driven representation was activated earlier on decay of the slow oscillatory inhibition ) .', 'However , as is apparent in the upper panel , this slight temporal separation was inadequate to segregate the signals for the purposes of selective representation in the higher area: cells selective for false conjunctions ( vertical-blue and horizontal-red ) were strongly activated .', 'Following the arrival of the burst of red/vertical inputs , synaptic and membrane time constants were sufficiently long to allow subsequent summation with the burst of blue/horizontal inputs , yielding the false activations .', 'We then considered the F-multiplexing state ( Fig 7B , middle panel ) , implemented as above via the inclusion of feedback inhibition between the different cells in the higher area .', 'The underlying activity in the lower area was completely unchanged , thus the first major event on decay of the slow oscillatory inhibition was again a synchronized burst of activity in the red-selective and the vertical-selective cells , which duly drove the vertical-red selective cell in the higher area .', 'This activation led to inhibition of the other cells in the higher area , so that they were unresponsive when the second ( horizontal-blue ) burst of activity arrived: by selectively processing the most salient item only , other re
['Introduction', 'Results', 'Discussion', 'Models']
['Several theories have been advanced to explain how cross-frequency coupling , the interaction of neuronal oscillations at different frequencies , could enable item multiplexing in neural systems .', 'The communication-through-coherence theory proposes that phase-matching of gamma oscillations between areas enables selective processing of a single item at a time , and a later refinement of the theory includes a theta-frequency oscillation that provides a periodic reset of the system .', 'Alternatively , the theta-gamma neural code theory proposes that a sequence of items is processed , one per gamma cycle , and that this sequence is repeated or updated across theta cycles .', 'In short , both theories serve to segregate representations via the temporal domain , but differ on the number of objects concurrently represented .', 'In this study , we set out to test whether each of these theories is actually physiologically plausible , by implementing them within a single model inspired by physiological data .', 'Using a spiking network model of visual processing , we show that each of these theories is physiologically plausible and computationally useful .', 'Both theories were implemented within a single network architecture , with two areas connected in a feedforward manner , and gamma oscillations generated by feedback inhibition within areas .', 'Simply increasing the amplitude of global inhibition in the lower area , equivalent to an increase in the spatial scope of the gamma oscillation , yielded a switch from one mode to the other .', 'Thus , these different processing modes may co-exist in the brain , enabling dynamic switching between exploratory and selective modes of attention .']
['There is a growing consensus that neuronal oscillations constitute a fundamental computational mechanism in the brain .', 'Beyond this , recent experimental evidence has highlighted interactions between oscillations at high and low frequencies ( e . g . gamma oscillations , 40–80 Hz , are modulated by theta oscillations , 4–10 Hz ) , and two major theories have developed regarding the functional role of this kind of cross-frequency coupling .', 'Here , we present a computational modelling study of these theories with strong implications for biological studies .', 'Firstly , we demonstrate for the first time that each of these theories is physiologically plausible , in that they can be implemented in a spiking network model with parameters guided by experimental data .', 'Secondly , we show that they are each computationally useful , able to overcome a feature-binding ambiguity in a presented stimulus .', 'Finally , we implement both theories within a single network model , and find that only a single parameter change is required to switch between the two processing states .', 'This leads to the exciting new proposal that both theories may be correct , both implemented in the brain , with dynamic switching between modes according to processing and attentional requirements .']
['medicine and health sciences', 'action potentials', 'neural networks', 'engineering and technology', 'nervous system', 'membrane potential', 'social sciences', 'electrophysiology', 'neuroscience', 'telecommunications', 'network analysis', 'interneurons', 'vision', 'multiplexing', 'computer and information sciences', 'animal cells', 'cellular neuroscience', 'psychology', 'cell biology', 'anatomy', 'synapses', 'physiology', 'neurons', 'biology and life sciences', 'cellular types', 'sensory perception', 'neurophysiology']