Campos, Michael

Segraves, Mark A.

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Michael Campos

Mark A. Segraves

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Signal Multiplexing in Neural Circuits – The Superior Colliculus Deserves a New Look

INTEGRATIVE NEUROSCIENCE
Signal multiplexing in neural circuits – the superior  
colliculus deserves a new look
Michael Campos1† and Mark A. Segraves2*†
1 Department of Neurosurgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
2 Department of Neurobiology and Physiology, Northwestern University, Evanston, IL, USA
*Correspondence: m-segraves@northwestern.edu
†Michael Campos and Mark A. Segraves have contributed equally to this article.
The primate superior colliculus (SC) is a 
key component of the system controlling 
voluntary movements of the eyes and head. 
A longstanding view is that the SC main-
tains a retinotopic representation of visual 
space, and issues commands specifying 
movements referenced to the fovea. While 
an accurate representation of target posi-
tion relative to the fovea is crucial to gaze 
shifts, information about the position of the 
eyes in their orbits is important to a number 
of potential SC functions that include deter-
mining the relative contributions of eye and 
head movements to generate gaze move-
ments, integrating multimodal sensory 
input, and generating sequences of multiple 
movements. Nevertheless, the existence and 
potential role for eye position signals in the 
SC remains controversial.
Adding to a growing body of evidence 
for an eye position role in SC function, a 
recent paper by Groh (2011) makes clever 
use of microstimulation to demonstrate 
an effect of orbital position of the eyes on 
the magnitude of saccades evoked from 
the monkey SC. Although earlier reports 
revealed an eye position dependency for 
electrically evoked saccades in both cats and 
monkeys (Roucoux et al., 1980; Segraves 
and Goldberg, 1992; Cowie and Robinson, 
1994; Freedman et al., 1996; Martinez-
Trujillo et al., 2003), whether the effects of 
stimulation implied the presence of an eye 
position signal in the SC remained unclear. 
Groh’s report is significant because it com-
pares the effects of two different stimula-
tion frequencies, yielding greater insight 
into possible mechanisms, and provides a 
theoretical framework to help explain the 
presence and purpose of an eye position 
signal in the SC.
Groh’s results suggest that an eye posi-
tion signal modulates the readout of sac-
cade commands issued from the SC. The 
effect of the eye position signal was great-
est when low frequency stimulation was 
delivered, and weaker, though still present 
at slightly higher stimulation frequencies. 
Some early reports utilized still higher 
stimulation frequencies, such as 500 Hz 
(Robinson, 1972; Schiller and Stryker, 
1972). Consistent with the trend observed 
by Groh, at these higher frequencies the 
effect of eye position is weaker still or 
entirely absent. While stimulation effects 
are notoriously difficult to interpret, Groh 
argues that these results confirm the exist-
ence of an eye position signal in the SC, 
and she further argues that the eye posi-
tion signals should be incorporated into an 
accurate model of saccade generation. Two 
variations of a revised saccade generation 
model are proposed. Both acknowledge the 
existence of an eye position signal within 
the SC, but they differ in three ways: (1) 
how the putative eye position signal relates 
to well-characterized saccade vector signals 
in the same area, (2) whether that signal is 
enhanced or diminished by electrical stim-
ulation, and finally (3) how and where that 
eye position signal is utilized downstream. 
In the first model (shown in Figure 10 of 
Groh), the direction of eye movement sen-
sitivity is anti-correlated with the direction 
of saccade vector tuning in the same area. 
The electrical stimulation enhances the 
eye position signal. This signal is then sub-
tracted from (or ignored by) the subsequent 
stage of eye movement processing in a “nor-
malization” step, and then added back at a 
later stage. Because of the anti-correlation, 
the result is a shorter than expected sac-
cade. In the second model (Figure 11), the 
eye movement sensitivity is positively cor-
related with saccade vector tuning in the 
same area. Electrical stimulation serves to 
“clamp” or block the existing eye movement 
signal. Downstream areas then attempt to 
decode a signal that is lacking the expected 
eye position component. Because of the posi-
tive correlation, the end result is again a 
shorter saccade.
Seemingly conflicting physiological 
reports provide evidence in support of both 
of these models. Paré and Munoz (2001) 
found that eye position sensitivity was 
anti-correlated with the directional selec-
tivity of co-present saccade vector signals 
in support of the first model. In support of 
the second model, Van Opstal et al. (1995) 
and Campos et al. (2006) found that eye 
position sensitivity was positively correlated 
with saccade vector tuning. However, as 
discussed in Groh (2011), these studies 
utilized different tasks. The analysis inter-
vals used may have also contributed to the 
conflicting findings. Importantly, Paré and 
Munoz (2001) analyzed buildup activity 
that occurred close to the beginning of a 
saccade, in a task in which the monkeys 
were expected to have a strong re- centering 
bias. By continuously measuring the 
strength of saccade vector and eye position 
tuning, Campos et al. (2006) found that eye 
position sensitivity was strongest at times 
far removed from the saccade, and that the 
eye position signal strength decreased as 
the saccade onset approached. The natu-
ral scanning paradigm in the latter study 
may also have diminished the strength of 
a re-centering bias. Future physiological 
studies will be needed to characterize the 
strength of eye position signals in various 
task conditions.
Just as the physiological literature does 
not definitively resolve differences between 
the models offered by Groh, neither does 
the current understanding of the effect of 
electrical stimulation. If stimulation serves 
to enhance an already present eye position 
signal, the model shown in Figure 10 is sup-
ported. If stimulation, instead, serves to sup-
press the normally present eye movement 
signal, then the model shown in Figure 11 
is supported. There is a growing body of 
evidence that electrical stimulation can 
either facilitate or suppress activity depend-
ing on the location of the stimulation, 
Frontiers in Integrative Neuroscience www.frontiersin.org March 2011 | Volume 5 | Article 5 | 1
OpiniOn Article
published: 31 March 2011
doi: 10.3389/fnint.2011.00005
general studies of how different signals are 
combined or efficiently juggled in neural 
circuits (Stein and Meredith, 1993).
Groh’s article taken another way suggests 
a form of frequency-division multiplexing 
in the SC. Whereas high frequencies may 
convey an eye-movement signal in purely 
retinotopic coordinates, lower frequencies 
might approach the “carrier frequency” of 
the eye position signal. In support of this 
idea, Corneil et al. (2007) have shown that 
low frequency stimulation can produce head 
movements without eliciting eye move-
ments. That is, “sub-threshold” frequen-
cies (below the threshold at which saccade 
are evoked and therefore encoded) might 
carry or encode pure head-movement sig-
nals. The tantalizing possibility is that the 
threshold at which a saccade is evoked is 
really more of a transition between these 
two frequency bands that carry signals to the 
different effectors. Pursuing this thread still 
further, the data from Campos et al. (2002) 
suggest a form of time-division multiplex-
ing within the SC. In natural scanning of 
images, the time around the saccades were 
found to encode a purely retinotopic signal, 
but during fixation intervals, other relevant 
signals, such as eye position were expressed 
in the available bandwidth. Subthreshold 
stimulation to the SC has also been shown to 
modulate cognitive factors, such as attention 
(Cavanaugh and Wurtz, 2004), presumably 
through interactions with upstream areas.
One of the main attractions to the study 
of the eye movement system, and the SC in 
particular, has been its perceived simplic-
ity. The oculomotor system has a relatively 
small number of moving parts, the eyes are 
light and easy to move, and the topographic 
map of eye movement vectors is elegantly 
arranged. With the growing evidence that 
the SC carries a diversity of signals, that it 
participates in cognitive functions in con-
junction with upstream areas, and influ-
ences the coordination of multiple effectors 
with downstream areas, the attraction of the 
SC for future years may, instead, stem from 
an appreciation of its complexity.
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Deisseroth, K. (2005). Millisecond-timescale, geneti-
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Spike triggered averaging of natural scanning reveals 
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Even with additional data points to 
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and downstream, electrical stimulation 
will always remain difficult to interpret. 
Advances in novel neural stimulation 
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The influences of eye position signals 
reported by Groh have important impli-
cations for some of the most fundamental 
questions in neuroscience. First, they pro-
vide new evidence that the SC contains neu-
ral circuitry capable of coordinating action 
plans (e.g., of the eye and head). Further 
study could reveal general mechanisms of 
effector coordination, similar to eye-hand 
coordination, or perhaps even sharing 
similarities with mechanisms of perceptual 
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ing to cognitive factors, the SC might reveal 
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multiplexed within neural circuits.
A representation of current eye position 
is just one of the many signals that converge 
on the SC. Given the simplicity of the sac-
cade vector map in SC, and the body of work 
that has established its function and ana-
tomical connections, it is an ideal structure 
to understand the subtle effects of a second 
type of signal as it modifies the dominant 
saccade vector command signal. This criti-
cal sensorimotor structure may be ideal for 
 stimulus parameters including  frequency, 
and  current behavioral state (for a review, 
see Johnson et al., 2008).
To fully understand the stimulation 
results, it is critical to consider the addi-
tional effects of low frequency stimulation 
that were reported by Groh. At eccentric 
initial eye positions, saccades were evoked 
less reliably and usually at a longer latency. 
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gated the effects of electrical stimulation 
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more pronounced effects at lower frequen-
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varied the initial eye position, while using 
a fixed stimulation frequency and current, 
and achieved the same trend. This sug-
gests that changes in initial eye position 
effectively modify the threshold at which 
saccades are evoked. It will be fruitful to 
characterize these effects by finely vary-
ing both the initial eye position and the 
stimulation frequencies and current, to 
understand whether and how eye position 
affects the threshold at which a saccade can 
be evoked.
Groh’s first model posits that when 
firing rates are very high, there is a “nor-
malization” process that occurs. When 
normalization does not occur individual 
spikes can be thought of as contributing a 
vote for a given eye movement vector. At 
higher frequencies the spikes are normal-
ized such that the votes are submitted as 
a percentage of the total. This mechanism 
can account for the precise specification 
of saccade direction and magnitude at 
each SC site. That is, very high frequen-
cies of activity do not produce increasingly 
larger magnitude saccades (although they 
do produce shorter latency, more reliable 
saccades). A normalization step is consid-
ered unnecessary for the second model 
(Figure 11). We propose, however, that 
the stimulation frequencies at which the 
normalization process is triggered should 
be considered a second threshold, in 
addition to the threshold at which a sac-
cade is evoked. Once the normalization 
“threshold” is crossed, the effects of eye 
position on the saccade vector readout are 
strongly inhibited. Therefore, a normaliza-
tion process could remain in the second 
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Received: 11 March 2011; accepted: 21 March 2011; pub-
lished online: 31 March 2011.
Citation: Campos M and Segraves MA (2011) Signal mul-
tiplexing in neural circuits – the superior colliculus deserves 
a new look. Front. Integr. Neurosci. 5:5. doi: 10.3389/
fnint.2011.00005
Copyright © 2011 Campos and Segraves. This is an open-
access article subject to a non-exclusive license between the 
authors and Frontiers Media SA, which permits use, dis-
tribution and reproduction in other forums, provided the 
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Campos and Segraves Signal multiplexing in neural circuits
Frontiers in Integrative Neuroscience www.frontiersin.org March 2011 | Volume 5 | Article 5 | 3


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