S-cone Visual Stimuli Activate Superior Colliculus Neurons in Old World Monkeys: Implications for Understanding Blindsight
Nathan Hall and Carol Colby Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021
Abstract ■ The superior colliculus (SC) is thought to be unresponsive calibrated psychophysically in each animal and at each in- to stimuli that activate only short wavelength-sensitive cones dividual spatial location used in experimental testing [Hall, (S-cones) in the retina. The apparent lack of S-cone input to N. J., & Colby, C. L. Psychophysical definition of S-cone stim- the SC was recognized by Sumner et al. [Sumner, P., Adamjee, uli in the macaque. Journal of Vision, 13, 2013]. We recorded T., & Mollon, J. D. Signals invisible to the collicular and magno- from 178 visually responsive neurons in two awake, behaving cellular pathways can capture visual attention. Current Biology, rhesus monkeys. Contrary to the prevailing view, we found 12, 1312–1316, 2002] as an opportunity to test SC function. The that nearly all visual SC neurons can be activated by S-cone- idea is that visual behavior dependent on the SC should be specific visual stimuli. Most of these neurons were sensitive impaired when S-cone stimuli are used because they are in- to the degree of S-cone contrast. Of 178 visual SC neurons, visible to the SC. The SC plays a critical role in blindsight. If 155 (87%) had stronger responses to a high than to a low S- the SC is insensitive to S-cone stimuli blindsight behavior cone contrast. Many of these neuronsʼ responses (56/178 or should be impaired when S-cone stimuli are used. Many clini- 31%) significantly distinguished between the high and low cal and behavioral studies have been based on the assumption S-cone contrast stimuli. The latency and amplitude of responses that S-cone-specific stimuli do not activate neurons in the SC. depended on S-cone contrast. These findings indicate that Our goal was to test whether single neurons in macaque SC stimuli that activate only S-cones cannot be used to diagnose respond to stimuli that activate only S-cones. Stimuli were collicular mediation. ■
INTRODUCTION blindsight pathway requires the LGN of the thalamus. Blindsight is an enigma. Patients with lesions in primary When the LGN is inactivated in awake, behaving monkeys visual cortex (V1) are unable to describe or perceive that have V1 lesions, extrastriate activation and blindsight stimuli in their blind field, yet they retain the ability to behavior are both abolished (Schmid et al., 2010). The detect, localize, and discriminate unseen stimuli (Cowey, SC and retina project to the LGN, which projects directly 2010; Weiskrantz, 2004; Sanders, Warrington, Marshall, to extrastriate cortex. After removal of V1, this pathway & Wieskrantz, 1974). This perplexing phenomenon has remains intact and is vital to blindsight behavior (Leopold, been demonstrated in both humans and monkeys (Gross, 2012). Moore, & Rodman, 2004; Stoerig & Cowey, 1997; Cowey An important strategy in studies of blindsight in humans & Stoerig, 1995; Moore, Rodman, Repp, & Gross, 1995). has been to block visual input to the SC psychophysically. Many researchers have investigated the capabilities and It is widely believed that the SC does not receive input mechanisms of blindsight, yet the pathways involved from short wavelength sensitive cones (S-cones) in the remain only partially understood (Leopold, 2012). retina (Sumner, Adamjee, & Mollon, 2002). The reason- Multiple cortical and subcortical structures contribute to ing is that, by using S-cone stimuli, visual pathways that blindsight. Projections from the superior colliculus (SC) to depend on the SC should be blocked or impaired. Several extrastriate cortex play a critical role in producing neuronal studies have used S-cone stimuli to test whether the SC visual responses in the absence of V1 (Gross, 1991). The mediates blindsight in humans (Alexander & Cowey, SC and extrastriate visual cortex are both crucial for blind- 2010; Leh, Ptito, Schönwiesner, Chakravarty, & Mullen, sight (Cowey, 2010; Yoshida, Takaura, Kato, Ikeda, & Isa, 2010; Tamietto et al., 2010; Marzi, Mancini, Metitieri, & 2008; Weiskrantz, 2004; Goebel, Muckli, Zanella, Singer, Savazzi, 2009; Leh, Mullen, & Ptito, 2006). Experimental & Stoerig, 2001; Vaughan & Gross, 1969). A possible paradigms have ranged from target detection to fMRI ac- tivation. The results have demonstrated selective impair- ments when S-cone stimuli are used as compared with University of Pittsburgh luminance stimuli. The conclusion is that the SC is likely
© 2014 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 26:6, pp. 1234–1256 doi:10.1162/jocn_a_00555 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 to be responsible for visual abilities demonstrated by The University of Pittsburgh Institutional Animal Care blindsight patients. and Use Committee approved all experimental protocols. Beyond blindsight, many behavioral studies have been Monkeys weighed 13 and 8.5 kg (monkey CA and mon- based on the assumption that S-cone isolating stimuli key FS, respectively). Both had normal trichromatic color do not drive cells in the SC. If this were true, the use of vision as evidenced by their ability to make saccades to S-cone isolating stimuli would be a convenient way to L-cone and S-cone isolating stimuli (data not shown). assess collicular function. This strategy was first proposed Each monkey underwent sterile surgery to implant an
in an influential behavioral study of SC function (Sumner acrylic cap with an embedded head restraint bar, scleral Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 et al., 2002). Since its inception, this technique has been search coils, and a recording chamber as described else- used in a number of human psychophysical studies of where (Dunn, Hall, & Colby, 2010). We used MRI to the SC. The appeal of this method is that the SC can be guide correct placement of the SC recording chambers, “lesioned” without any damage to the brain, making it which were positioned posteriorly on the midline at useful in healthy human volunteers. Many studies using an angle of 40°. The SC was located approximately 25– S-cone stimuli have found differences in behavioral re- 30 mm below the surface of the brain. sponses to S-cone as compared with luminance stimuli. When behavioral effects are observed, the interpretation Data Acquisition is that the SC must play a critical role in the affected behavior. During experiments, animals sat in a primate chair The original idea that the SC is blind to S-cone isolating with head fixed. Monkeys viewed a CRT monitor at a stimuli is based on anatomical and physiological studies. distance of 30 cm. Eye position was monitored using Early physiology studies found that SC neurons and the scleral search coils ( Judge, Richmond, & Chu, 1980) with retinal ganglion cells that form the retinotectal pathway a Riverbend field driver and signal processing filter are not color opponent and are not sensitive to S-cones (Riverbend Instruments, Inc., Birmingham, AL). Eye posi- (De Monasterio, 1978b; Marrocco & Li, 1977; Schiller & tion voltages were continuously monitored on-line through Malpeli, 1977). The corticotectal pathway in turn carries NIMH Cortex software (provided by Dr. Robert Desimone) information originating only from the magnocellular and saved for off-line analysis of saccades on a separate layers of the LGN. Neurons in the magnocellular layers computer running Plexon software at a sampling rate of carry summed inputs from long and middle wavelength 1000 Hz (Plexon, Inc., Dalls, TX). Neuronal spiking activity sensitive cones (L- and M-cones), but not S-cones. Single was recorded using tungsten microelectrodes (Frederick neurons in monkey SC are silenced when the magno- Haer, Bowdoinham, ME) inserted into the SC through cellular layers of the LGN are inactivated (Schiller, Malpeli, stainless steel guide tubes stabilized in a nylon grid system & Schein, 1979). The conclusion is that SC neurons should (Crist Instrument Co., Hagerstown, MD). Voltage signals be responsive to achromatic luminance stimuli but not to were amplified, filtered, and sorted using on and off-line chromatic stimuli. template-matching and PCA (Plexon, Inc., Dalls, TX). The No single neuron studies have directly tested whether collicular surface was physiologically identified by the cells in the SC respond to individually calibrated S-cone sudden appearance of light sensitive neuronal activity as isolating stimuli. Studies of SC afferents only make clear the electrode was advanced. At deeper locations, eye that these afferents are not color opponent and not movement-related activity was observed. Visual and motor whether SC neuronal responses are affected by calibrated receptive fields were in agreement with known SC maps S-cone isolating stimuli. One recent study reported neuro- (Goldberg & Wurtz, 1972; Schiller & Stryker, 1972). Trial nal sensitivity in the SC of macaques to colored stimuli types, events, and outcomes were monitored with Cortex (White, Boehnke, Marino, Itti, & Munoz, 2009). Another software and stored with neuronal spike data at 40 kHz has reported the absence of S-cone input in the marmoset using Plexon hardware and software. SC (Tailby, Cheong, Pietersen, Solomon, & Martin, 2012). Our goal was to test directly whether S-cone isolating Stimulus Presentation and Control stimuli can activate single cells in the SC of awake, behav- ing macaque monkeys under conditions that explicitly Stimulus timing and presentation were controlled using replicate those used in human behavioral and clinical NIMH Cortex software. Stimuli were presented on a research. Surprisingly, our data show that S-cone-specific 19-in. ViewSonic color CRT monitor at a refresh rate of stimuli produce robust activation of SC neurons. 85 Hz using an 8-bit DAC with an ATI Radeon X600 SE graphics card. To generate stimuli, the monitor was cali- brated for color and luminance using a Photo Research PR-655 SpectraScan spectroradiometer integrated with METHODS custom MATLAB (Mathworks, Natick, MA) software. The Two adult male rhesus monkeys (Macaca mulatta) were accuracy of the calibration was verified by independently used in these experiments. Animals were cared for in measuring the spectral composition of all stimuli used. accordance with National Institutes of Health guidelines. Stimulus colors were chosen from MacLeod–Boynton
Hall and Colby 1235 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 (MB) color space (MacLeod & Boynton, 1979) as defined presented on such a background are therefore detectable using the Smith and Pokorny cone fundamentals (Smith only through contrasts falling outside the range of the & Pokorny, 1975). noise. The luminance of the squares was uniformly dis- tributed across nine possible values ranging from 18.78 to 22.55 cd/m2, spaced in increments of approximately Stimuli and Background 0.5 cd/m2. The mean background luminance across all We presented stimuli defined by either luminance or possible values was 20.73 cd/m2, with mean color co-
S-cone contrast. In MB space, S-cone excitation is iso- ordinates in MB space of (0.66692, 0.01493) as compared Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 lated along a vertical vector, perpendicular to the with the theoretical value (0.66667, 0.01500). L- and M-cone excitation axis, known as the tritan vector. The goal of our experiment was to test SC neuronal re- The actual tritan vector varies across individuals and sponses to S-cone-specific stimuli. We converted stimuli to spatial locations because of variations in cone density DKL contrast space to make the effects of contrast in color and macular pigment (Hall & Colby, 2013; Sumner opponent channels explicit (Brainard, 1996; Derrington, et al., 2002; Snodderly, Auran, & Delori, 1984; Snodderly, Krauskopf, & Lennie, 1984). The mean color and lumi- Brown, Delori, & Auran, 1984). We presented S-cone nance of the background noise in MB space was used stimuli chosen from psychophysically calibrated tritan as the basis point to convert stimuli to DKL space. This vectors determined separately for each spatial location procedure gives stimulus contrasts with respect to the and each animal (Hall & Colby, 2013). Briefly, our calibra- mean color and luminance of the EEG noise background. tion approach takes advantage of “transient tritanopia” Conversion to DKL space gives contrasts corresponding (Smithson, Sumner, & Mollon, 2003; Mollon & Polden, to the luminance mechanism (L + M), the L- and M-cone 1975). The principle is that sensitivity in the S-cone op- opponent mechanism (L − M) and the S-cone opponent ponent channel is briefly and selectively decreased after mechanism [S − (L + M)], that is, the S-cone isolating adaptation to a bright yellow background. Elevated L- and direction. Following the procedure described by Brainard M-cone channel activity persists after excessive stimula- (1996), we normalized DKL space such that a stimulus tion by the bright yellow background, which causes isolating a specific mechanism in DKL space with unit selective desensitization of S-cone opponent pathways. pooled cone contrast (i.e., the length of the 3-D vector Elevated L- and M-cone activation means that greater in cone contrast space equals one) would correspond S-cone excitation is needed to outweigh them and thus to a contrast of 100%. This normalization procedure detect a true S-cone isolating stimulus. That is, detection has the advantage that it is independent of observer threshold is increased for S-cone isolating stimuli. The and experimental setup. We define the DKL coordinate increase in threshold is greatest for the stimulus that contrasts for each mechanism as a vector of the form best matches the exact S-cone isolation point for a given (L + M, L − M, S − (L + M)). In these terms, the viewer. The calibrated individual and location-specific minimum contrast of the luminance noise background tritan vector is defined as the vector in MB color space was (−16.2298, 0.0091, 1.0320), and the maximum was most desensitized after adaption to a bright yellow (15.3497, −0.0402, −0.2187). background. Three stimulus types were presented on the back- The calibrated tritan vector for each monkey and ground array of squares: luminance, high-contrast spatial location examined was rotated to the right of the S-cone, and low-contrast S-cone. Stimuli were 1° × 1° theoretical vertical tritan line in MB space. Calibrated squares embedded in the luminance noise background. tritan vectors were brought into congruence with standard The luminance contrast stimulus (24.92 cd/m2) isolates MB space by linearly transforming their MB values such the luminance mechanism (35.1922, 0.1817, 0.5641). that the calibrated tritan vector extends vertically and This stimulus is more than double the maximum lumi- orthogonal to the standard L- and M-cone excitation axis. nance contrast of the noise background. The other two We were able to identify four location-specific tritan vec- stimuli activated the S-cone opponent mechanism. One tors in monkey FS and four in monkey CA using our pro- was a high S-cone contrast stimulus whose DKL coordi- cedure outlined above (Hall & Colby, 2013). Neurons in nates across all three mechanisms ranged from (−5.4318, the SC with receptive fields corresponding to these cali- 0.0157, 95.7475) to (−8.7634, −0.1684, 95.9704). The brated locations were targeted in each animal, and all stim- other was a low S-cone contrast stimulus whose DKL ulus presentations took place at these calibrated locations. coordinates ranged from (−2.7450, 0.0462, 28.3539) to Stimuli were presented on an equal energy gray (EEG) (−6.2916, −0.2824, 29.5714). Both S-cone stimuli slightly background of luminance noise (Sumner et al., 2002; decreased DKL luminance contrast and contained only Birch, Barbur, & Harlow, 1992). The background was a full small, inconsistent contrasts in the DKL L-M opponent screen array of 1° × 1° squares whose color was EEG but mechanism. Such small and inconsistent deviations in whose individual luminances changed at random every mechanisms other than the S-cone opponent channels four monitor frames (∼47 msec). This flickering back- would not be expected to produce consistent effects ground removes potential artifacts created by stimuli that on neurons. Luminance and L-M opponent contrasts are not exactly equiluminant with the background. Stimuli remained within the range covered by the background
1236 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 noise. S-cone stimuli presented on the noisy background sented on a dark background (<0.01 cd/m2). These stim- were therefore detectable only on the basis of S-cone uli represent the maximum contrast possible with our contrast and are thus S-cone isolating stimuli. The high- monitor. At the beginning of each trial, a 1° × 1° fixation contrast S-cone and luminance stimuli were chosen to be cross appeared and the monkey fixated for 200–400 msec. similar to those found in previous human psychophysics While maintaining fixation, a 0.5° diameter circle was pre- research. The low-contrast S-cone stimulus was chosen sented in the recorded neuronʼs receptive field for four to lie near the luminance stimulus and far from the high- frames (∼47 msec). Monkeys were required to maintain – contrast S-cone stimulus in DKL space. fixation for an additional 300 500 msec after stimulus Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 In 10 neurons, we additionally tested neuronal re- presentation before the fixation cross was turned off, sponses to an L-cone stimulus as defined in DKL space cueing the animals to make a saccade to the remembered (data not shown). SC neurons were responsive to the location of the target. Saccades within approximately 1.5° L-cone stimulus, as found previously (White et al., 2009). of the target location were rewarded with a drop of liquid. This confirmed that our results are not specific to S-cone Data for the MGS task were collected in a block of 20 trials stimuli or a subpopulation of SC neurons, but that SC before the fixation task and a block of 20 trials after the neurons can be broadly activated by different cone inputs. fixation task.
Behavioral Tasks Fixation Task We used a standard memory-guided saccade (MGS) task At the beginning of each trial, a 1° × 1° black (<0.01 cd/m2) to identify neurons with receptive fields at locations at fixation cross was presented as the luminance noise- which tritan vectors had been calibrated (Hall & Colby, masking background was introduced. Animals fixated the 2013). We tested each SC neuron in two tasks. We used central cross for 200–400 msec (Figure 1, left), after which the MGS task to classify neurons as visual or visuomotor. one of the three stimulus types was presented. The stim- We then used a fixation task to measure neuronal re- uli appeared for four frames (∼47 msec) synchronously sponses to the luminance and to high- and low-contrast with the change in the luminance noise background (Fig- S-cone stimuli. During previous S-cone calibration ses- ure 1, center). The figure shows the high-contrast S-cone sions, S-cone stimuli were behaviorally relevant because stimulus, outlined in white for clarity. This outline was they served as saccade targets for the animals (Hall & not present during the actual task. All three stimuli were Colby, 2013). In the fixation task of these experiments, relatively difficult for a human observer to detect. After no response was required after stimulus presentation. stimulus presentation, animals were required to continue fixating for an additional 200–400 msec to receive a liquid reward. After the additional fixation period, the luminance MGS Task noise and fixation cross were turned off and the intertrial During MGS trials, the stimulus and fixation point were interval (ITI) began (Figure 1, right). During the 400-msec maximum monitor intensity white (63.15 cd/m2)pre- ITI, an EEG screen approximately equal to the average
Figure 1. Fixation task and average neuronal responses to background luminance noise and stimuli. Upper schematics show fixation task timing and paradigm. Center task schematic shows only the presentation of the high-contrast S-cone stimulus highlighted with a white outline, which is not present during the actual task. Neuronal responses are average spike density functions across all three stimulus types. Neurons were classified as sustained visual (SV), transient visual (TV), sustained visuomotor (SVM), and transient visuomotor (TVM). Left: During the ITI the screen is steady EEG. The luminance noise background is turned on, and at the same time a fixation cross appears. Middle: After 200–400 msec of fixation, a stimulus appears in the recorded neuronʼs receptive field. The stimulus was either a high-contrast S-cone, low-contrast S-cone, or luminance contrast. Right: The animal fixates for an additional 200–400 msec after stimulus presentation to receive a liquid reward.
Hall and Colby 1237 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 background noise (−0.7879, 0.0000, 0.4667) was dis- presentation across all 40 trials of the MGS task and played. This procedure minimizes the contrast between performed a fast Fourier transform on the average spike the ITI background and the luminance noise background train. From the Fourier transform, we computed the onset. The ITI screen also served to maintain the animals average power at frequencies from 2 to 100 Hz as the in a primarily photopic visual state because its luminance baseline power. This frequency band was chosen because was relatively high (20.66 cd/m2). Fixation trials were run it contains spiking activity from neurons with high base- in a separate block from the MGS task. The three stim- line firing rates (strong low frequency components) and
ulus types were presented randomly interleaved with neurons with low, spurious baseline firing rates (strong Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 20 presentations of each stimulus type. Stimuli were pre- high frequency components). We then computed the sented in the recorded neuronʼs receptive field at the average power at frequencies from 13 to 30 Hz as the calibrated tritan vector locations for each animal (Hall & stimulus power. This stimulus frequency band was chosen Colby, 2013). Possible stimulus locations were located because it captures our stimulus frequency of 21.25 Hz radially from fixation at an eccentricity of 4° for monkey (refresh rate divided by stimulus frames, i.e., 85/4) and FS and 6° for monkey CA. encompasses the frequency power exhibited by neurons whose responses closely tracked stimulus presentation with on and/or off responses. Transience indices were Data Analysis then computed as the ratio: (stimulus power)/(stimulus We analyzed trial event timing, eye position, and spike power + baseline power). Thus, a neuron whose average timing. All analyses were carried out off-line using custom baseline power was equal to its average stimulus power MATLAB software (Mathworks, Natick, MA). would have a transience index of 0.5. Neurons with tran- sience indices of >0.5 were classified as transient and those of ≤0.5 were classified as sustained. Neuron Classification Neurons in the superficial layers of the SC have visual Neurons were classified by responses during the MGS task. responses that are generally transient (White et al., 2009; Averageneuronalfiringrateduringthebaselineepoch Marrocco & Li, 1977; Schiller & Koerner, 1971). In this (−100 to 0 msec before stimulus presentation) was com- study, 20/31 visual neurons classified as transient were pared with average activity during the visual response confirmed to lie near the collicular surface (less than epoch (30–130 msec after stimulus presentation) and 1 mm). Visual neurons deeper than 1 mm had sustained saccade epoch (−50 to 50 msec after saccade onset, or transient responses, and at greater depths visuomotor defined as the time at which eye velocity first exceeded neurons predominated. 30°/sec). Of 194 neurons recorded, 178 showed a sig- nificant visual response (one-sided t test, p < .05) and were Spike Density Function included in further analysis. Of these neurons, 91 also had a significant saccade-related response (one-sided t test, Average spike density functions (SDFs) were computed p < .05) and were classified as visuomotor neurons. The by placing spikes across all trials from all neurons in remaining 87 neurons were classified as visual. 0.1-msec bins. The resulting nonnormalized histogram Visual and visuomotor neurons were further classified was then convolved with a Gaussian kernel using a as having transient or sustained visual responses by com- 2-msec standard deviation and values were converted puting a transience index. Previous studies have measured to firing rates in spikes per second. transience by comparing peak firing rate during a defined response epoch to average activity in the following epoch Neuronal Response Latency (White et al., 2009; Schiller & Malpeli, 1977). Our sam- ple contained many cells exhibiting a strong response to Neuronal response latency was determined by finding stimulus offset as well as stimulus onset (e.g., Figure 2, the time to half height of the peak response for each Row 2). Neurons with clear on–off responses were gen- neuron (Lee, Williford, & Maunsell, 2007). To find the erally transient in nature. Their on response must end peak response, we computed the SDF for each neu- before the off response begins to produce a distinct off ron but using a 5-msec Gaussian kernel, which produces response. Because of their off response, these cells have greater smoothing and reduces spurious results. We iden- high levels of activity in the epoch following the initial tified the time of SDF peak firing rate in the window response. Using previous approaches (White et al., 2009; from 40 to 150 msec after stimulus onset. The peak time Schiller & Malpeli, 1977), such neurons were often clas- was used to find the last point in time the SDF crossed sified as sustained neurons, although their responses threshold before reaching its response peak. Threshold appeared very transient. We therefore used a different was set at half the peak value plus the average SDF rate method for determining transience based on the Fourier from 200 to 0 msec before stimulus onset. The time at transform of each neuronʼsspiketrains.Webinnedthe which the firing rate last crossed threshold before reach- spike trains (0.1 msec time bins, i.e., 10,000 Hz sampling ing its peak was defined as the neuronal response latency. rate) of each neuron from −200 to 300 msec after stimulus For some neurons, the response to one of the stimulus
1238 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021
Figure 2. Rasters and histograms from example neurons in each of the four cell classes. The MGS task was used to classify neurons (left columns). Neuronal responses to the three stimuli were then recorded during the fixation task (right columns).
types was absent or very small, so that an accurate half were computed from spikes in the interval 40–200 msec height could not be determined in the prescribed window. after stimulus presentation. These indices provide a mea- We required that a response latency was determined for all sure of each neuronʼschangeinresponsetothestimulus three stimulus types to eliminate any bias caused by not types compared. Values of zero indicate equal response including latency to all stimulus types from all neurons. and positive values indicate stronger response to the Neurons whose response latency to all three stimulus high-contrast S-cone stimulus. types could not be determined were omitted from fur- ther latency analysis (15/56 SV, 8/31 TV, 12/66 SVM, and 7/25 TVM neurons were omitted). Statistical Analyses In the analyses on mean firing rates, we computed the mean firing rate for each neuron in the window from Contrast Sensitivity Indices 40 to 200 msec after stimulus presentation. When using For each neuron, we measured how its responses differed peak firing rates, we chose the same peak used for the across the three stimulus types. To do this, we computed latency analysis: maximum firing rate of the SDF for a two contrast sensitivity indices: a high versus low S-cone single neuron in the window from 40 to 150 msec after contrast sensitivity index and a high S-cone versus lumi- stimulus onset. Peak firing rates were analyzed because, by nance contrast sensitivity index. These indices were com- definition, sustained neurons have longer responses than puted as (HighS − LowS)/(HighS + LowS) and (HighS − transient neurons. This could lead to a systematic bias Luminance)/(HighS + Luminance) where HighS, LowS, toward sustained neurons exhibiting greater mean re- and Luminance indicate the mean firing rate of the neuron sponses when comparisons are made across cell classes. to the respective stimulus types. The mean responses We report analyses on peak firing rates primarily to make
Hall and Colby 1239 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 across class comparisons and include the same analyses affected single unit responses, average activity, peak on mean firing rates for comparison. activity, and neuronal response latency. For comparisons across trials within a single neuron, we used a one-way ANOVA on mean firing rates of single trials. For comparisons of firing rate across neurons with- SC Neuronal Responses Modulate with in a class, we found the mean response of each neuron S-cone Contrast across trials and used a one-way repeated-measures Single Neurons Respond to S-cone Stimuli
ANOVA to account for the firing rate differences across Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 neurons. For comparisons of neuronal response latency We divided SC neurons into four classes. First, we used across neurons within a class, we used the nonparametric the MGS task to classify neurons as visual or visuomotor. Friedman test, which is comparable to a one-way repeated- Of 194 neurons recorded, 178 showed significant visual measures ANOVA. responses during the MGS task. Of these, 91 showed To compare population firing rates of all neurons across significant saccade responses and were classified as visuo- classes (SV, TV, SVM, and TVM), we performed a two-way motor. The remaining 87 were classified as visual. Second, ANOVA on both mean and peak firing rate with factors of we classified neurons as either sustained or transient based Cell Class and Stimulus Type. This procedure allowed us to on their visual response profile in the MGS task. Neurons compare across all neurons in an unbalanced design and from all four cell classes responded to the luminance and gives a measure of the interaction effect between cell S-cone contrast stimuli. class and stimulus type. The interaction statistic is used Characteristic responses of neurons from each class to test whether neurons in different classes responded are shown in Figure 2. The example sustained visual (SV) differently to the three stimulus types. To compare neuro- neuron (Figure 2, top row) responded to stimulus onset nal response latency across classes, we wanted to continue and had no response during the saccade in the MGS task. using nonparametric tests and so chose to compare the In the fixation task, this neuron fired less to the low- latency across all four classes one stimulus type at a time. contrast S-cone stimulus than to the luminance and high To this end, we used the Kruskal–Wallis test, which is com- contrast S-cone stimuli (one-way ANOVA, HSD, both p < parable to a one-way ANOVA. All post hoc comparisons .05). The transient visual (TV) neuron (Figure 2, second were made using Tukeyʼs honestly significant difference row) showed very brief responses to both stimulus onset test for multiple comparisons, denoted HSD. For correla- and offset. Like the SV neuron, this TV neuron fired less tion analyses, we used Pearsonʼs correlation coefficient to the low-contrast S-cone stimulus than the other two and the t statistic for significance testing. stimuli ( p < .05). The example visuomotor (SVM and TVM) neurons (Figure 2, bottom 2 rows) had saccade related activity in the MGS task. The TVM neuron re- RESULTS sponded more briskly to stimulus presentation than did We found that single neurons in macaque SC are activated the SVM neuron. The example visuomotor neurons were by S-cone isolating stimuli. We measured the visual re- sensitive to all three stimulus types but did not signifi- sponse characteristics of SC neurons to a luminance and cantly distinguish among them ( p > .05). Similar response two S-cone contrast stimuli, a high and low S-cone contrast. patterns were observed across the population of SC neu- The prevailing hypothesis is that SC neurons cannot be rons (Table 1). A total of 56/178 visual neurons responded activated by any S-cone isolating stimulus. We tested re- significantlymoretohighthantolowS-conecontrast sponses to two different S-cone contrasts because if SC stimuli. Most of the other neurons responded to all stim- neurons truly respond to S-cone contrast, their responses ulus types, but response differences did not reach sig- should change as S-cone contrast changes. We used a lumi- nificance. The two S-cone stimuli were closely matched nance noise background to eliminate luminance artifacts in their luminance contrast, differing only in their ability during a fixation task (Figure 1, upper schematics). Stimuli to excite S-cone sensitive visual inputs. These data show were presented at screen locations at which S-cone isolat- that most SC neurons respond to S-cone stimuli and ingstimulihadbeencalibratedineachanimal.Atthe that the activity of many SC neurons distinguishes S-cone beginning of each trial, SC neurons responded weakly to contrast. the onset of the luminance noise background (Figure 1, lower plots). After the response to onset of the checkered All Cell Classes Are Sensitive to S-cone Contrast background, neurons slowly adapted their firing rates, as shown previously for repeatedly stimulated SC neurons We asked whether each class of SC neurons was able (Boehnke et al., 2011; Marrocco & Li, 1977; Cynader & to discriminate the three stimulus types. The average Berman, 1972). After adaptation SC neurons exhibited SDF responses to each stimulus for neurons in the four sustained firing rates slightly above the baseline response classes are shown in Figure 3. All classes exhibited dif- during the ITI. Presentation of a visual stimulus embedded ferential mean responses to the three stimulus types in the luminance noise elicited a large visual burst. In the that were highly significant (repeated-measures one-way sections below, we report how S-cone-specific contrasts ANOVA, each p < .0001). Average firing rate for each
1240 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 Table 1. Number of Neurons in Each Class that Discriminated between One or More of the Stimulus Types
Class Total Total Sig High > Low High > Lum Lum > Low SV 56 26 18 6 13 TV 31 12 9 2 6 SVM 66 23 18 4 13
TVM 25 14 11 6 4 Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021
High and Low refer respectively to the high-contrast and low-contrast S-cone stimulus responses. Lum refers to the luminance stimulus response. Counts in the Total column are the total number of neurons in each of the four classes. Counts in the Total Sig column are the number of neurons that showed significant response differences to the three stimulus types (one-way ANOVA, p < .05). The three rightmost columns show the number of neurons in each class with significant differences in mean response between the stimulus types indicated in the top row (post hoc, TukeyʼsHSD, p < .05). Neurons in the three rightmost columns are subsets of Total Sig but are not mutually exclusive.
class strongly and significantly differentiated between the .999), indicating that the three stimuli were treated high- and low-contrast S-cone stimuli (all classes, HSD, uniformly by all four cell classes. p < .001). In addition, all classes preferred the luminance We were concerned that using mean responses could stimulus to the low-contrast S-cone isolating stimulus (SV, affect our analysis of the interaction between class and TV, and SVM neurons, HSD, p < .001; TVM neurons, HSD, stimulus type. The mean response of transient neurons p < .05). We conclude that each class of neurons, taken as is likely to be weaker than that of the sustained neurons a whole, modulates their response with S-cone contrast. in a large time window because sustained neurons were defined to have greater response duration. Indeed, the two-way ANOVA on average firing rates showed a strong Stimulus Response Modulation Is Similar across main effect of Cell Class ( p < .0001), which would be Cell Classes expected if sustained neurons fired more spikes to the We were especially interested in whether the different stimuli than transient neurons. Post hoc comparisons neuron classes responded differently to each stimulus revealed that SVM cells had stronger responses than type, as has been reported for luminance and color stim- both transient classes whereas SV neurons exceeded uli (White et al., 2009). To see how response modulation the response of TV neurons (HSD, all p < .05). Yet the might differ across the four cell classes, we performed a average peak responses of each cell class are qualitatively two-way ANOVA on the mean neuronal responses using congruent (Figure 3). White et al. (2009) reported a factors of Stimulus Type and Cell Class. To assess whether peak firing rate modulation of SC neuronal responses all cell classes were similarly modulated by the three to colored stimuli. It is possible that many SC neurons stimulus types we looked at the interaction between Class distinguish the stimuli by modulation of their peak firing and Stimulus. The result was highly nonsignificant ( p = rate rather than mean rate.
Figure 3. Average SDFs for responses to the three stimulus types (luminance, black; high-contrast S-cone, dark blue; low-contrast S-cone, light blue). Sustained neurons are shown in the left column, and transient neurons are in the right column. Visual neurons are shown in the top row, and visuomotor neurons are in the bottom row. All SDFs are aligned on stimulus presentation.
Hall and Colby 1241 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 We performed a second two-way ANOVA on the peak contrast stimuli can evoke stronger responses than a low- firing rates of the SC neurons to address this issue. The contrast luminance stimulus. analysis showed that peak firing rate differences are invar- iant across cell classes (main effect of Class, p =.4950). We again saw that the four cell classes treated the three SC Neuronal Response Latency Modulates with stimulus types similarly in their peak response modula- S-cone Contrast tion (interaction of class and stimulus, p =.9973).Thus, All Classes Shift Neuronal Response Latency with
differential responses to the three stimuli over the popula- Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 tion of SC neurons are independent of cell class. S-cone Contrast It is typical of visual neurons to modulate both response magnitude and latency as a function of contrast. As con- SC Population Responses Differentiate All Three Stimuli trast increases, latency decreases. If SC neurons are truly We wanted to know whether SC responses to S-cone sensitive to S-cone contrast, their response latency stimuli could be greater than those to luminance at the should change as S-cone isolating contrast changes. We population level. The two-way ANOVA on mean responses plotted cumulative distributions of neuronal response revealed a strong effect of Stimulus Type across all four latencies for each class of neuron and found that this was classes of SC neurons (main effect of Stimulus, p = indeed the case (Figure 4). Within each class, response .0153). Post hoc analysis revealed that this discrimination latency was significantly modulated across the three stim- − was the same as for within class comparisons: Response ulus types (Friedman test, all classes p <1.0×10 6). to the high-contrast S-cone stimulus was significantly Neuronal response latencies to high-contrast S-cone and greater than the low (HSD, p < .05) but not the lumi- luminance stimuli were much shorter than to the low- nance stimuli (HSD, p > .05), whereas response to the contrast S-cone for all classes (HSD, both p <.01).Inad- luminance stimulus did not differ significantly from the dition, the TV neurons had significantly shorter latency low S-cone contrast (HSD, p >.05).Theresultswere responses to the high-contrast S-cone than to the lumi- similar and even stronger when peak responses were nance stimulus (HSD, p < .05). These results mirror those analyzed (main effect of Stimulus, p = .0001). Post hoc found with neuronal activity, namely, that responses to analysis further confirmed that peak firing rate modulation the high-contrast S-cone stimulus significantly differed follows the same pattern as mean firing rate modula- tion. Peak responses are greater to the high- than low- contrast S-cone stimulus (HSD, p < .001), whereas peak responses to the luminance versus low S-cone and lumi- nance versus high S-cone were not significantly different (HSD, p >.05). The population SDF response for each cell class is stronger for the high-contrast S-cone stimulus than the luminance stimulus (Figure 3). Yet these differences were not significant within any given class or in the two-way ANOVA pooling the SC population across classes. To de- termine whether these differences were significant, we performed an analysis that is not confounded by variance across neurons. Because neuronal responses across cell classes did not significantly differ in their modulation by stimulus type, we discarded the factor of class and per- formed a repeated-measures one-way ANOVA on the en- tire population of 178 SC neurons. In this analysis, we are not sorting by cell class, and the irrelevant variance across neurons is eliminated. The only effect under inquiry is that of stimulus type. We found that the high-contrast S-cone stimulus response was greater than the luminance, which in turn exceeded the low-contrast S-cone stimulus response (HSD, all p < .001). This pattern was identical and even more striking when peak activation was consid- Figure 4. Cumulative distributions of neuronal response latency. − ered instead of mean response (HSD, all p <1.0×10 9). Conventions are the same as in Figure 3. Colored numbers and Together these results show that the most important vertical lines indicate the median response latency to each corresponding stimulus type. Neurons are drawn from the same characteristics to SC neurons are the total contrast of population and cell classes as in Figure 3. Neurons were excluded stimuli, regardless of the types of cones excited. Responses if the response to at least one stimulus type was too weak for scale with S-cone contrast and sufficiently high S-cone latency analysis (see Data Analysis in Methods).
1242 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 from those to the low-contrast S-cone stimulus within S-cone Contrast Sensitivity Increases each cell class. with Transience Throughout the visual system, there is a tendency for TV neurons to be more sensitive to changes in contrast. We Neuronal Response Latency Shifts Are Greater for asked whether this would be true of SC neurons using Visual Neurons S-cone isolating contrasts. We plotted the high versus Given that all classes had response latencies modulated low S-cone contrast sensitivity index of each neuron by S-cone contrast, we wanted to know whether there were against its transience index separately for visual and visuo- Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 any differences across the neuron classes. To that end, motor neurons (Figure 5, top row). Nearly all neurons we compared the neuronal latency distributions to each tested had a stronger mean response to high- than to stimulus type across the four cell classes. We found that low S-cone contrasts (73/87 visual and 82/90 visuomotor neuronal latency to the luminance and low-contrast S-cone contrast sensitivity indices > 0). This shows that although stimuli were roughly the same across classes (Kruskal– only about 1/3 of neurons significantly distinguished the Wallis, p = .0563 and p = .1759, respectively). For the two contrasts (Table 1), nearly all neurons increased their high S-cone contrast stimulus, neuronal latencies differed response as S-cone contrast increased. In addition, the significantly (Kruskal–Wallis, p = .0169), with SV neurons degree to which neurons modulated their response with responding earlier than SVM neurons (HSD, p < .05). S-cone contrast was correlated with their level of tran- Although this comparison yielded the only significant dif- sience (visual cells, r = 0.2121, p = .0486; visuomotor ference, neuronal latency differences to the luminance cells, r = 0.2885, p = .0058). SC neurons with more tran- stimulus across cell classes approached significance. It is sient responses were more sensitive to changes in S-cone likely that our sample of transient neurons was inadequate contrast. to detect any small differences in latency between TV and visuomotor neurons. Furthermore, because stimuli that S-cone Contrast Sensitivity Is Weaker elicit the largest visual responses (the high S-cone and than Luminance luminance stimulus) produced the greatest differences across classes, nonlinearities in contrast sensitivity be- In addition to response modulations with S-cone contrast, tween transient and sustained neurons may have obscured we asked how the high-contrast S-cone stimulus responses differences between neuronal classes. Qualitatively, the compared with those to the luminance stimulus. We exam- median latencies of the TV neurons were all less than or ined this question by plotting the high S-cone versus lumi- equal to those of the TVM neurons. These data suggest nance contrast sensitivity index of each neuron against its that visual neurons may respond sooner than visuomotor transience index separately for visual and visuomotor neu- neurons to high-contrast stimuli, although the differences rons (Figure 5, bottom row). These data indicate that appear small. SC neuronal responses were much more similar for the high S-cone and luminance stimuli than between the two S-cone stimuli (45/87 visual and 55/91 visuomotor contrast SC Population Neuronal Response Latencies sensitivity indices > 0). Correlations for visual and visuo- Differentiate All Three Stimuli motor neurons in this instance were not significant (visual cells, r = 0.2001, p = .0631; visuomotor cells, r = 0.0732, Finally, we wondered whether the small differences seen p = .4907), although visual neurons trend in the positive in median response latency between the luminance and direction. The contrast of the high S-cone stimulus was high-contrast S-cone stimuli were meaningful at the popu- much greater than the luminance in DKL space. The con- lation level, independent of cell class. To increase statisti- trast of the low S-cone stimulus was only slightly less than cal power, we grouped response latencies across all cell the luminance stimulus contrast. Our results indicate that classes, despite the possibility of small differences in SC neurons as a whole treated the high S-cone and lumi- neuronal response latency between visual and visuomotor nance stimuli as being more similar than the low S-cone neurons. This analysis yielded a highly significant result for and luminance stimuli, in opposition to their definition in latency differences across the stimulus types (Friedman, − DKL space. These data suggest that overall SC neurons p <1×10 33). Further analysis confirmed that response may be more sensitive to luminance contrast than to latencies to each of the three stimulus types significantly S-cone contrast. Nevertheless, response magnitude can differed from one another (HSD, all p < .001). In particu- bemadegreaterorsmallertoanS-conecomparedwitha lar, the neuronal response latencies to the high-contrast luminance stimulus by appropriately manipulating contrast. S-cone stimulus were shorterthantotheluminance stimulus. SC neurons within each class responded with shorter latency to high than to low S-cone contrasts. At DISCUSSION the class-independent population level, increasing S-cone contrast elicited responses with shorter latency compared Neurons in the SC are sensitive to S-cone isolating stim- with the luminance contrast stimulus. ulus contrasts. SC visual responses are a function of total
Hall and Colby 1243 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 Figure 5. Contrast sensitivity indices as a function of transience index. Top row: High versus low S-cone contrast sensitivity index. Each point plots a neuronʼs contrast sensitivity index against its transience index. Colors indicate each neuronʼs classification as visual or Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 visuomotor. Filled circles indicate neurons classified as sustained, and open circles indicate neurons classified as transient. Solid black lines are the least squares linear regression line of best fit. Dashed horizontal black lines correspond to a contrast sensitivity index of 0, indicating equal responses to high- and low-contrast S-cone stimuli. Bottom row: High S-cone versus luminance contrast sensitivity index. Conventions are the same as top row.
cone contrast that does not discriminate against S-cones. Early Studies of SC Visual Afferents and Properties This finding raises questions about the visual properties In early studies, the ganglion cells comprising the direct, of and visual inputs to SC neurons. It has a direct bearing retinotectal pathway were reported to lack chromatic on studies that have used S-cone isolating stimuli to probe sensitivity. Pioneering physiological investigations of the the role of the SC in visual and oculomotor phenomena, direct pathway to SC recorded retinal ganglion cells, such as blindsight. studied their properties, and confirmed tectal projection by antidromic activation from the SC (De Monasterio, 1978a, 1978b; Schiller & Malpeli, 1977). They found How Could Information about S-cone Stimuli that direct projections to SC arose primarily from non- Reach the SC? opponent ganglion cells that sum input from L- and There are two major pathways by which visual input from M-cones. SC-projecting ganglion cells had transient re- the retina reaches neurons in the SC. The SC receives sponses and generally lacked a strong center-surround direct input from retinal ganglion cells, primarily to the organization. Many of these ganglion cells were classified superficial layers (Marrocco & Li, 1977; Bunt, Hendrickson, as the broad band type now associated with the magno- Lund, Lund, & Fuchs, 1975; Hubel, LeVay, & Wiesel, 1975; cellular “luminance” pathway. The conclusion was that Hendrickson, Wilson, & Toyne, 1970). It also receives in- the direct pathway to the SC carries primarily or exclusively direct, cortical input from striate and extrastriate cortex. luminance contrast information from L- and M-cones. Striate cortex targets more superficial neurons, whereas Cortical projections to the SC also appear to stem from extrastriate cortex targets the intermediate and deeper luminance channels in the LGN (Finlay, Schiller, & Volman, layers (Sommer & Wurtz, 2004; Fries, 1984; Kuypers & 1976). Antidromically activated corticotectal neurons in V1 Lawrence, 1967). Either or both of these pathways could are mostly complex cells that have large receptive fields, contribute to the collicular activation we observed using weak orientation selectivity and lack color opponency. S-cone stimuli. Lesion or cooling of striate cortex causes a powerful,
1244 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 selective decrease in visual sensitivity of neurons in deeper searchers reported a population of “rarely encountered SC layers while sparing sensitivity of the superficial layers cells” with small axons and slow conduction velocity (Schiller, Stryker, Cynader, & Berman, 1974). Similar defi- that projected to the SC in unusually high proportions. cits were found after inactivation of the magnocellular Another early report on retinal ganglion cells that pro- layers of the LGN, but not the parvocellular layers, where ject to SC called them “atypical,” with on and off re- color opponent neurons are found (Schiller et al., 1979). sponses to visual stimuli and nonconcentric receptive The conclusion was that visual inputs to the SC from striate fields (De Monasterio, 1978b). These cells seem to cor-
cortex arise from the magnocellular layers of the LGN, sum- respond well with earlier reports of less numerous non- Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 ming achromatic signals from L- and M-cones in the retina. concentric ganglion cells with phasic responses, large The properties of neurons projecting to the SC through receptive fields, and no color opponency (De Monasterio both the direct and indirect pathways are reflected in & Gouras, 1975). Although not color opponent, some of those of visual SC neurons (Marrocco & Li, 1977; Cynader these cells responded well to stimuli of any color, as do & Berman, 1972; Goldberg & Wurtz, 1972). Visual neu- visual neurons in the SC (White et al., 2009; Marrocco & rons in the SC have comparatively large receptive fields Li, 1977). Some atypical ganglion cells were reported to with a weak or absent inhibitory surround. They are rela- receive input from all cone types and even project directly tively insensitive to stimulus size, shape, orientation and to the SC (De Monasterio, 1978a). More recent studies lack color opponency. Observations of SC neurons and have confirmed these findings, revealing a heterogeneous their primary visual inputs have led to the belief that SC population of numerous ganglion cell types that project to neurons do not get input from S-cones. the SC (Rodieck & Watanabe, 1993; Perry & Cowey, 1984; Leventhal et al., 1981). Many properties of SC projecting ganglion cells closely resemble those of ganglion cells “Rarely Encountered Cells” known to carry S-cone-related signals to the koniocellular Initial reports on both direct and indirect pathways showed layers of the LGN (Dacey & Packer, 2003; Hendry & Reid, a lack of color opponent input with no contribution from 2000). Chromatic sensitivity in the SC could arise from S-cones. From an evolutionary perspective, the lack of this small population of ganglion cells that have proven S-cone input to the SC is a curious finding. Both the especially difficult to characterize. SC (Kaas, 2004) and S-cones are evolutionarily ancient (Mollon, 1989). The SC shares similarities across many Recent Characterization of S-cone Input to Retinal mammalian species, and the ganglion cell types that carry Ganglion Cells S-cone signals in modern primates were more prominent in early primates (Kaas, 2004). Genes encoding the S-cone Advances in technique have allowed targeted, intracellular in macaques and humans are highly homologous and recordings of retinal ganglion cells. Targeted recording conserved across mammals, although not all mammals led to the identification of the first class of ganglion cell express this gene (Yokoyama & Yokoyama, 1989; Nathans, that carries S-cone-specific signals (Dacey, 1996; Dacey Thomas, & Hogness, 1986). Across new and old world & Lee, 1994). Modern tracing techniques allow morpholo- monkeys, systems for opponent S-cone vision appear con- gical identification of recorded neurons. Targeted re- served, again hinting at its early origins among primates cording combined with chromatic adaption and silent ( Jacobs, 2007; Silveira et al., 1999), with the notable substitution (older studies used monochromatic lights exception of some new world species (Levenson, Fernandez- to study color opponency, not cone isolation techniques) duque, Evans, & Jacobs, 2007; Jacobs, 1998). The conser- allows physiological characterization of cone inputs in vation of S-cones and the SC in mammals would appear addition to anatomical imaging (Dacey, 1999). Without to make their interaction likely. these methods, it is difficult to measure cone-specific Why have S-cone inputs to the SC gone undetected? input, especially if S-cone input is weak, and nearly im- The most likely explanation stems from the properties possible to classify ganglion cell types (Dacey, Peterson, of the S-cone subsystem. S-cones, and the ganglion cells Robinson, & Gamlin, 2003; Klug, Herr, Ngo, Sterling, that carry their output are rare in the retina, comprising & Schein, 2003; Calkins, 2001). It is now known that only about 5–10% of cells (Calkins, 2001; Bumsted & a diverse population of ganglion cells carries both Hendrickson, 1999). Ganglion cells that project to the S-cone on and off inputs to the more recently recognized SC are also scarce and tend to have broad, sparse dendritic koniocellular layers of the LGN, which lie between the fields (Rodieck & Watanabe, 1993; Perry & Cowey, 1984; magnocellular and parvocellular layers (Szmajda, Buzas, Leventhal, Rodieck, & Dreher, 1981). To make matters FitzGibbon, & Martin, 2006; Hendry & Reid, 2000; Martin, worse, ganglion cells carrying S-cone signals are a hetero- White, Goodchild, Wilder, & Sefton, 1997). Most SC pro- geneous population that tend to have small axons and low jecting ganglion cells have been classified as the P gamma firing rates (Hendry & Reid, 2000). As noted by Schiller cell type (Perry & Cowey, 1984). This heterogeneous and Malpeli (1977), these properties are likely to create population is most commonly associated with the diverse a severe bias against detecting such ganglion cells in non- cell types that receive S-cone input and project to the targeted extracellular recordings. Nevertheless, these re- koniocellular layers of the LGN. Whether the cells so far
Hall and Colby 1245 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 classified as receiving S-cone input also project to the SC is (White et al., 2009). Isoluminant Gaussian patches were not yet known. presented in the receptive field of SC neurons. The color There are a large number of cell types and cell-specific of the patches was chosen from across DKL space, includ- interactions in the retina whose properties are still being ing stimuli near and along the theoretical, uncalibrated, characterized (Dacey & Packer, 2003; Dacey, 1999). Efforts S-cone isolating direction. Recorded SC neurons were to study these interactions have revealed a variety of broadly sensitive to color, including colors that should sparse cell types that carry input from S-cones and are most strongly modulate the S-cone opponent mecha-
similarinmanyrespectstothoseknowntoprojectto nism. White et al. (2009) further reported that achromatic Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 the SC. Additional studies suggest that S-cones may in- stimuli produce shorter latency visual responses than fluence other visual subsystems more than originally be- chromatically defined stimuli. This latency result may re- lieved. For example, S-cones contribute to a number of flect the use of only a maximum contrast luminance stim- functions commonly associated with the luminance chan- ulus. We used a low-contrast luminance stimulus and nel, and it has been suggested that they may contribute varied the contrast of our chromatic S-cone stimulus. Our to this pathway (Calkins, 2001). S-cone OFF bipolar cells data show that, although low-contrast S-cone stimuli evoke have been found that contact midget ganglion cells and longer latency responses than luminance stimuli, a high- hence may influence the parvocellular pathway (Klug contrast S-cone stimulus can evoke shorter latency re- et al., 2003). Other research has uncovered bipolar cells sponses than a luminance stimulus. When comparing that could contact all cone types ( Joo, Peterson, Haun, chromatic versus achromatic response latency, stimulus & Dacey, 2011) and melanopsin-expressing ganglion cells contrast must be taken into account. Our results indicate that carry color signals derived from S-cones and may con- that neuronal responses in the SC are largely determined tribute to perception (Dacey et al., 2005). At least eight by a contrast-dependent broadband summation of cone other types of ganglion cells were recently discovered, activation that includes S-cones. representing only 1–2% of the population, and at least Sustained and transient SC neurons differ in their sensi- two of these are sensitive to S-cone-specific excitation tivity to color as compared with luminance (White et al., (Dacey & Packer, 2003; Dacey et al., 2003). In addition, 2009). White et al. (2009) found that TV neurons are much two more types of achromatic ganglion cells have been less sensitive to color than to luminance. We performed a reported that sum input from all cone types (Calkins & similar neuronal classification on our visual SC neurons. Sterling, 2007). Many of these cells have wide dendritic We found that the most transient neurons are more sen- fields, suggesting broad summation and large receptive sitive to changes in S-cone isolating contrast. Differences fields, as would be expected for SC projecting cells and between the high and low-contrast S-cone stimuli in the is common among koniocellular projecting cells (Szmajda, present results and the findings between the luminance Grünert, & Martin, 2008). Many other types of small and chromatic stimuli of White et al. (2009) are similar ganglion cells have been observed but await further clas- on the grounds of contrast. In both studies, TV neurons sification to determine their cone sensitivity and possible were more sensitive to contrast. Our data show that con- tectal projections (Crook, Peterson, Packer, Robinson, trast sensitivity is not specific to the particular visual Gamlin, et al., 2008; Crook, Peterson, Packer, Robinson, mechanism activated by the stimulus. We conclude that Troy, et al., 2008). Ongoing research makes it clear that TV neurons are more sensitive to contrast than sustained the types of cells and signals leaving the retina are not fully neurons and this includes chromatic sensitivity to S-cone understood. Some of these newly discovered ganglion input. cell types or those yet to be fully characterized could be the source of S-cone input observed in the SC. Chromatic Sensitivity in Marmoset SC Interesting recent investigations in new world monkeys Comparisons to Previous Results on S-cone measured cone input to SC neurons in anesthetized Related Excitation in the SC marmosets, with emphasis on input from S-cones (Tailby Several previous studies have examined the effect of color et al., 2012). S-cone responses were observed only after and S-cone stimuli on visual responses in the SC. These presentation of flashed S-cone stimuli. These responses studies have used a variety of techniques. None have used were typically weak, although the S-cone response was S-cone stimuli calibrated individually for each observer stronger to stimulus offset. The relatively weak response and spatial location combined with dynamic luminance of SC neurons to S-cone stimuli was attributed to re- noise. Our focus was on using techniques from human sidual contrast in long wavelength cones and not true psychophysics to make our results directly comparable. S-cone input. When drifting gratings were used to mea- sure response characteristics of SC neurons, responses to changes in S-cone contrast were not observed. The authors Chromatic Sensitivity in Macaque SC concluded that SC neurons are not driven by S-cones. Only one previous study has investigated color sensitivity Residual contrast in longer wavelength cones seems in SC neurons recorded in awake, behaving macaques insufficient to account for our data. The SC neurons we
1246 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 recorded frequently exhibit on and off responses to world and old world monkeys in their S-cone and konio- S-cone stimuli. These responses are as large as those to cellular layer organization ( Jacobs, 2007; Hendry & Reid, stimuli designed to specifically modulate contrast in the 2000). Especially of interest here is that the projection long wavelength sensitive cones. We used two levels of from SC to koniocellular LGN neurons appears stronger S-cone contrast and, across animals and spatial locations, in macaques than in new world monkeys, suggesting presented six radiometrically distinct S-cone stimuli. The possible differences for the role of S-cone input and tectal effects of these stimuli on the luminance and L-M op- influence between these species (Hendry & Reid, 2000).
ponent channels were small and, because of limitations The observation that S-cone input was not present in the Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 of the 8-bit DAC, inconsistent across stimuli. S-cone stim- marmoset SC could be a result of either of these factors. uli were presented on a checkered background that was constantly changing luminance to mask residual responses Chromatic Sensitivity in Human SC in luminance channels by deliberately creating luminance contrast artifacts (Birch et al., 1992). Because the monitor How are physiological resultsinmonkeysreflectedin calibration is not perfect and equiluminant points vary human fMRI responses? This question has been directly between neurons (Schiller & Colby, 1983), the noise had addressed in two recent studies. In both studies, S-cone small additional effects on L-M opponent channels. Yet isolating stimuli were presented while measuring fMRI we observed consistent and large SC neuronal response activation in the SC. Leh et al. (2010) compared activation modulation with changes in S-cone contrast. Considering to achromatic and S-cone stimuli where the achromatic that our use of luminance noise is, by design, better suited stimulus was of greater cone contrast. They found that to control for residual luminance effects than L-M oppo- activation of the SC was absent using S-cone compared nent effects, it is worth noting what would be expected with achromatic stimuli (Leh et al., 2010). Interestingly, of residual L-M opponent activation. The L-M opponent a second fMRI study appears to have measured a BOLD channel is slower than the luminance channel, both psycho- signal response change to S-cone stimuli in the same physically and electrophysiologically (Bompas & Sumner, direction as luminance stimuli during pro and antisaccade 2008; Smithson & Mollon, 2004; Schmolesky et al., 1998; tasks (Anderson, Husain, & Sumner, 2008). Their effect Maunsell & Gibson, 1992). This suggests that it would take suggests stronger activation to luminance than to S-cone a large amount of residual L-M opponent contrast for SC stimuli that were matched for subjective salience. The neurons to exhibit shorter response latencies to the high- conclusion from both studies was that the human SC is contrast S-cone stimulus than to the luminance stimulus. not activated by S-cone isolating stimuli. Taken together with the relatively large response magnitude Three major concerns arise when considering fMRI to chromatic stimuli observed in our data and in that of activation of the SC to visual stimuli. (1) The SC is a dif- White et al. (2009), it is difficult to attribute our responses ficult structure to measure using fMRI (Anderson & Rees, entirely to residual activation of L- and M-cones. 2011), although rough topography and visual responses The conclusion that S-cone input does not reach the SC have been measured (Schneider & Kastner, 2005; DuBois is surprising when one considers the other physiological & Cohen, 2000). (2) Visual responses in the SC rapidly and anatomical aspects of this structure. In addition to habituate (Tailby et al., 2012; Boehnke et al., 2011), their analysis of cone inputs, Tailby et al. (2012) rigorously which is likely to reduce measured visual responses given characterized the temporal, spatial, and direction prefer- the temporal resolution of fMRI. (3) The final and most ences of SC neurons in a way not previously done. They important concern is stimulus contrast. Our data and found that spatiotemporal properties of SC neurons more those from other studies (Bell, Meredith, Van Opstal, & closely match those of koniocellular layer neurons, which Muñoz, 2006; Schneider & Kastner, 2005) demonstrate are known to receive input from S-cone-sensitive ganglion that contrast has a major effect on SC activation. Even when cells, than those of the magnocellular or parvocellular cone contrast is matched, it is difficult to make com- layers, which do not. These data in isolation would pre- parisons between cone mechanisms (Brainard, 1996), dict the presence of S-cone input to the SC if neuronal particularly because the luminance mechanism shows a responses are largely a reflection of the properties of their steeper, saturating CSF (Tailby et al., 2012; Tailby, Szmajda, afferent visual neurons. Buzas, Lee, & Martin, 2008). Data from these two fMRI Two major differences in experimental procedure com- studies rely on changes relative to activation during a lumi- pared with the awake, behaving macaque model were nous background presentation and not absolute activity. noted by Tailby et al. (2012). (1) Their subjects were This would make it easy to miss responses in the SC to anesthetized and the effects of anesthesia are prejudiced S-cone stimuli that are weaker than responses to other against cortical structures. Such an effect could dispropor- stimuli. Indeed, it appears Leh et al. (2010) observed dimin- tionately reduce cortically dependent color sensitivity in ished responses to the S-cone stimulus in several visual the SC. (2) Despite their many similarities to macaques, areas, and both studies show weak activation of the SC, it is possible that new world marmoset monkeys have which could be accounted for by differences in contrast. organizational differences in their visual system. This pos- In summary, direct tests of input to the SC show a sibility is emphasized by discrepancies between new number of differences likely to stem from the use of
Hall and Colby 1247 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 differentspeciesaswellasstimuluspresentationand responses are required but not in exogenous cueing of measurement techniques. Whether there are actually attention. large differences between species and stimulus presenta- The initial success in finding distinct outcomes with tion techniques requires further research. We chose to S-cone compared with luminance stimuli prompted fur- follow closely techniques used in human psychophysics ther studies. Inhibition of return is the tendency to avoid to relate our data to this line of work. Unlike previous returning to previously attended locations. Inhibition of studies in nonhuman primates, we calibrated S-cone return was absent when saccadic responses were re-
stimuli for each animal and spatial location and used a quired to a previously attended S-cone stimulus location Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 relatively strong luminance noise background to reduce (Sumner,Nachev,Vora,Husain,&Kennard,2004).In residual response artifacts. Our technique revealed contrast, inhibition of return was observed after attend- strong modulation of SC neurons with changes in S-cone ing an S-cone stimulus when manual responses were re- contrast that contradict several other findings. quired. This distinction suggested the possibility of two distinct mechanisms for inhibition of return: a saccadic mechanism mediated through the SC and a separate Blocking Visual Input to the SC with mechanism for manual responses independent of the SC S-cone Stimuli (Sumner, 2006). Beginning with the innovative work of Sumner and col- Continued use of S-cone isolating stimuli to block SC leagues (2002), many human psychophysical studies have input showed no effect of using S-cone isolating stimuli taken advantage of an apparent lack of S-cone input to on the gap effect and nasotemporal asymmetry (Bompas, explore the role of SC. The rationale for these experiments Sterling, Rafal, & Sumner, 2008; Sumner, Nachev, Castor- is that the SC can be effectively “lesioned” by using visual Perry, Isenman, & Kennard, 2006). The gap effect is seen stimuli that the SC cannot perceive. Collicular “lesions” are when a fixation target is extinguished before target presen- performed by presenting stimuli that are only detectable tation, providing a temporal gap between fixation release through use of retinal S-cones. Behavioral responses and motor response. The result is faster saccadic RT. to S-cone stimuli are then compared with those to lumi- Studies of the gap effect using S-cone stimuli as the fixa- nance stimuli to which the SC is not blind. If differences tion point were similar to those using a luminance defined (typically RT differences) are observed between behavioral fixation point (Sumner et al., 2006). Although fixation of responses to the S-cone and luminance stimuli, the con- the luminance stimulus provided a stronger effect, it could clusion is that the SC mediates the behavior under inves- not be ruled out that the gap effect was sensitive to S-cone tigation because the SC cannot resolve the S-cone stimulus. stimulus fixation. Nasotemporal asymmetry is seen when A negative result using S-cone stimuli (RTs to luminance observers, monocularly presented with two stimuli, pre- and S-cone stimuli are equal) is taken to mean that the ferentially choose the target in the temporal visual field. SC does not mediate the behavioral effect in question. This effect is thought to reflect an asymmetry in retino- Our data show that the assumption that the SC is insen- tectal projections. Nasotemporal asymmetry was found sitive to stimuli that activate only S-cones is incorrect. to be similarly present using both S-cone and luminance Nevertheless, several studies have reported behavioral defined targets (Bompas et al., 2008). Results from these effects using S-cone stimuli. two studies suggested that the SC does not play a pivotal The first experiments to use S-cone stimuli to block role in the gap effect or nasotemporal asymmetry. the SC reported distinct behavioral effects for luminance The idea that visual input to the SC could be blocked compared with S-cone stimuli. The first study to use or altered using S-cone stimuli, as cleverly set forth by S-cone stimuli to block visual input to SC investigated Sumner and colleagues, proved highly influential. Numer- two phenomena: the oculomotor distractor effect and ous other groups have used S-cone stimuli to investigate exogeneous orienting of attention (Sumner et al., 2002). SC function under the assumption that the SC is insensi- The oculomotor distractor effect is characterized by in- tive to S-cone stimuli. Phenomena studied range from creases in saccadic RT to a visual target when a second the redundant target effect (Leo, Bertini, di Pellegrino, & visual stimulus, the distractor, is presented elsewhere in La davas, 2008) and pro-antisaccade cost (Anderson et al., the visual field. Sumner et al. (2002) reported the absence 2008) to more clinical applications such as interhemi- of the oculomotor distractor effect when the distractors spheric transfer in callosotomy patients (Savazzi et al., were S-cone isolating stimuli. This result was found only 2007; Savazzi & Marzi, 2004) and mediation of blindsight for saccadic responses and not when manual responses (discussed below), among many others. were required. Exogenous orienting of attention is the phenomenon whereby an irrelevant stimulus briefly How Can Psychophysical Work Be Reconciled presented at the target location just before the go cue with the Current Results? decreases RT. In contrast to the distractor effect, S-cone and luminance cues both produced exogenous orienting Our experimental methods were modeled after human of attention. The conclusion was that the SC has a primary psychophysics studies using S-cone stimuli with the goal role in the oculomotor distractor effect when saccadic of testing the assumption that the SC is blind to S-cone
1248 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 stimuli. Yet our data show that SC neurons are respon- paradigm, saccade bias was measured through compari- sive to S-cone isolating stimuli under these conditions. sons within stimulus type. No behavioral differences were This means that the SC cannot be blocked by using an observed between S-cone and luminance stimuli when S-cone stimulus in this manner. the differential processing time of luminance and S-cone How could psychophysical studies find positive results stimuli did not affect the results. This further supports if S-cone activation does reach the SC? This is an impor- the conclusion that positive behavioral effects may have tant question given the widespread use of S-cone stim- underlying causes that stem from neuronal response
uli now present in the literature. Many of these studies latency and stimulus contrast, rather than the role of SC Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 did not use precisely measured or individually calibrated in the behavior. S-cone stimuli. They simply used “blue” or “purple” stimuli whose retinal activation properties are not known. Several S-cone and Luminance Processing Channels Differ also used low levels of luminance noise, which could lead to influence from rods. If we focus on those that closely The S-cone processing system appears slower than the follow the techniques proposed by Sumner and colleagues, luminance system. Several studies using S-cone stimuli there are two explanations. Both hinge on the fact that have attempted to account for confounds of stimulus nearly all psychophysical studies using the S-cone stimulus contrast by equating stimuli for subjective salience or technique rely heavily on RT measurements. objective contrast (Thirkettle et al., 2013; Anderson et al., 2008; Bompas & Sumner, 2008; Sumner et al., 2006). Nevertheless, differences in RT are often observed be- Stimulus Contrast Affects RT and Neuronal Response tween subjectively matched S-cone and luminance stimuli. It has long been known that RT is strongly dependent This could be attributed to differences in the S-cone op- on stimulus contrast or magnitude (Hovland & Bradshaw, ponent and luminance channels in the brain. Even sub- 1937). The response latency of SC neurons is largely de- jectively matched luminance and S-cone stimuli vary in termined by the luminance contrast of the stimulus (Bell, processing time psychophysically (Bompas & Sumner, et al., 2006). Our data extend this finding to include S-cone 2008; Smithson & Mollon, 2004). Physiologically, differ- isolating contrasts. Therefore, if S-cone and luminance ences are also observed in S-cone signal processing in V1 stimuli are not matched, RTs could vary as a simple matter (Cottaris & De Valois, 1998) and through retinal ganglion of contrast and neuronal latency. cells and koniocellular neurons in the LGN (Hendry & It is noteworthy that several studies found negative Reid, 2000). Estimates of these differences typically indi- results using S-cone stimuli when manual responses were cate that S-cone processing is about 20–40 msec slower required, but positive effects using saccadic responses. than luminance processing, which could have a substantial Saccadic eye movements are executed with shorter RT impact on measured RT. and greater velocity than typical manual responses. Our Some investigators using S-cone stimuli have acknowl- data demonstrate that neuronal latencies in the SC (as edged the differential processing of S-cone and luminance in other brain regions) are influenced by cone contrast. signals. Attempts to account for the slowness of the S-cone Furthermore, our data suggest that luminance signals system have involved manipulating cue timing and stim- are likely to reach the SC faster than S-cone signals of ulus onset asynchronies to allow more time for S-cone comparable strength. These small differences in trans- signal processing (Bompas & Sumner, 2009; Sumner mission time would be more likely to affect motor sys- et al., 2004). Indeed, this technique has revealed that, con- tems with simple, rapid processing like the saccadic eye trary to Sumner et al. (2002), the oculomotor distractor movement system. Thus, it is possible that manual and effect is present when S-cone stimuli are used (Bompas saccadic RTs are differentially influenced by S-cone stim- & Sumner, 2009). This finding validates the importance uli because of differences in timing precision, rather than of RT effects caused by stimulus contrast and processing their explicit use of the SC visual pathways. in separate visual channels. The combination of subjective Supporting the idea that contrast-dependent neuronal salience matching and stimulus onset asynchronies for response latency plays a critical role, the gap effect and S-cone stimuli appears to be a necessary and valuable tech- nasotemporal asymmetry showed no effect of S-cone nique for comparing RT between S-cone and luminance stimuli. In both tasks, the impact of differential processing stimuli. time between the luminance and S-cone stimulus is likely to be negligible. For the gap task, the fixation point is How Can Psychophysical Results Be Reinterpreted? turned off, and the subject has 200 msec to release fixation and prepare for the saccade. As long as this process takes Our finding that S-cone stimuli activate SC neurons less time than is actually allotted, differences in S-cone requires a reevaluation of results using such stimuli to and luminance processing time would not be reflected in block the SC. Despite the concerns raised above, there behavioral RT. The investigation of nasotemporal asym- are positive results demonstrating differences in the metry actually avoided confounds of direct comparison use of S-cone and luminance contrasts that are likely between luminance and S-cone stimuli entirely. Using this attributable to the use of S-cone stimuli. Instead of
Hall and Colby 1249 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 these psychophysical findings being directly attributable Neural responses in dorsal stream visual areas are less to the SC per se, they are likely a reflection of the S-cone affected by V1 lesions. This is because dorsal stream areas processing system itself. Three simple lines of evidence are able to utilize their input from the SC in the absence support the view that the S-cone and luminance systems of V1 (Gross, 1991). Neurons in the superior temporal should process stimuli differently. (1) The visual system polysensory area show reduced responses and selectivity can be subdivided into multiple distinct subsystems, after V1 lesions, but these responses break down com- where luminance and color are processed separately pletely after additional SC lesions (Bruce, Desimone, &
(Nassi & Callaway, 2009; Derrington, 2002). (2) Even Gross, 1986). Similarly, lesion or cooling of V1 alone Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 the individual chromatic channels have evolved sepa- has almost no effect on neurons in middle temporal rately for their own purposes, being distinct anatomically, (MT) area. However, when V1 lesions are combined with morphologically, and immunologically (Smithson & SC lesions, MT responses are eliminated (Rodman, Mollon, 2004). (3) Most importantly, the S opponent Gross, & Albright, 1989, 1990). system is known to exhibit a number of properties How are these neurophysiological observations related different from luminance and L-M opponent channels to blindsight? Reversible inactivation of the SC abolishes (Nassi & Callaway, 2009; Calkins, 2001; Hendry & Reid, blindsight behavior in monkeys with V1 lesions (Kato, 2000). On these grounds, behavioral and neuronal Takaura, Ikeda, Yoshida, & Isa, 2011). Interestingly, an response differences between S-cone and luminance SC lesion alone has little or no effect on either MT or stimuli should be expected independent of collicular MST neuronal responses, suggesting that removal of V1 mediation. Because our data show that S-cone stimuli are may enhance the role of the SC in visual function (Gross, able to drive SC neurons, previous results might be better 1991). Residual dorsal extrastriate activation has been interpreted in light of the peculiarities of the S opponent observed in both monkey and human blindsight sub- subsystem as a whole, rather than as an indicator of SC jects using fMRI (Schmid et al., 2010; Goebel et al., contribution. 2001). Studies of more expansive cortical lesions demon- strate that activity in dorsal stream extrastriate areas is important for blindsight. Lesions that include V1 and Implications for the Study of Blindsight extrastriate cortex deplete residual visual capacities and SC and Extrastriate Cortex Play a Role in Blindsight often eliminate blindsight (Leh et al., 2006; Weiskrantz, Blindsight is defined as the ability to detect, localize, 2004; Stoerig, Faubert, Ptito, Diaconu, & Ptito, 1996). and discriminate visual stimuli despite visual field defects In summary, extrastriate cortex and its input from the produced by damage to primary visual cortex (V1). The SC are likely to play a pivotal role in blindsight (Leopold, term is used to acknowledge the fact that patients with 2012; Yoshida et al., 2008; Gross et al., 2004). V1 lesions may have quite good residual visual capabilities despite their inability to report visual detection verbally Examining the Role of SC in Blindsight Using (Cowey, 2010; Weiskrantz, 2004; Sanders et al., 1974). Chromatic Stimuli Consistent with a lack of conscious awareness of visual stimuli, blindsight is distinctly different from impaired To pinpoint the role of the SC in blindsight, several inves- normal vision, such as near threshold detection (Azzopardi tigators have attempted to block visual input to the SC by & Cowey, 1997; Weiskrantz, 1986). Blindsight has been using colored stimuli. For example, the speeding of RT studied in both humans and macaque monkeys and is produced by redundant targets disappears in blindsight believed to be similar in both species (Gross et al., 2004; for both red and purple colored stimuli (Marzi et al., Stoerig & Cowey, 1997; Cowey & Stoerig, 1995; Moore 2009). A similar result was found while measuring pupil et al., 1995). Despite substantial efforts, the exact path- and fMRI responses (Tamietto et al., 2010). The conclu- ways and mechanisms responsible for blindsight are not sion is that the SC plays an essential role in blindsight be- completely resolved (Leopold, 2012). cause it is selectively discriminated against by the use of Many studies have suggested an essential role for the colored stimuli. These data stand in contrast to several SC in the mediation of blindsight (Leopold, 2012; Cowey, other investigations of the effects of color in blindsight. 2010; Yoshida et al., 2008; Weiskrantz, 2004; Gross, 1991; Numerous investigators have asked whether blindsight Vaughan & Gross, 1969). This evidence comes in large patients can discriminate any color at all. Their results part from early lesion studies. It has long been known provide an apparent contradiction with studies attempt- that ventral stream visual areas, like inferotemporal cortex, ing to block visual input to the SC in blindsight subjects are more dependent on visual input from V1 as compared using chromatic stimuli. Color opponency is present in with dorsal stream areas in parietal cortex (Vaughan & human blindsight (Stoerig & Cowey, 1989, 1991), and re- Gross, 1969). Visual responses in inferotemporal cortex sults are similar in macaques (Cowey & Stoerig, 1999). are abolished by V1 lesions (Rocha-Miranda, Bender, Results in monkeys and humans reveal a role for the Gross, & Mishkin, 1975) and visual discriminations S-cone opponent system and suggest that, if anything, dependent on ventral stream processing are impaired this system may be stronger in blindsight than the L-M (Cowey & Gross, 1970). opponent mechanism (Cowey & Stoerig, 2001). In fact,
1250 Journal of Cognitive Neuroscience Volume 26, Number 6 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 responses to green stimuliappearedtobeweakest S-cone stimuli. These findings are consistent with a role among the blue, green, and red stimuli tested. Effects for chromatic detection and the SC in blindsight. of color have also been observed via fMRI activations of the SC to red, but not green, stimuli (Barbur, Sahraie, Pathways for S-cone Signals in Blindsight Simmons, Weiskrantz, & Williams, 1998). Together, these studies support a role for color in blindsight (Stoerig & What are the pathways through which S-cone signals Cowey, 1997). Nevertheless, the effects of cone contrast could contribute to blindsight? From studies of neuronal
and luminance are difficult to resolve in these studies degeneration patterns, it might be expected that L-M Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 because stimuli were not specific to any cone or visual opponency would decline, whereas S opponency re- mechanism, specifically the S-cone mechanism. mained stable or strengthened (Stoerig & Cowey, 1997). After V1 lesions, there is widespread degeneration of LGN and retinal ganglion cells in pathways that carry S-cone Discrimination in Blindsight L- and M-opponent signals, whereas those in S-cone path- Precise cone activation was addressed more directly ways are less damaged (Cowey, Alexander, & Stoerig, 2011; using uncalibrated S-cone contrast stimuli (Leh et al., Cowey, 2010). This is presumably because afferent and 2006). In hemispherectomized subjects, these investiga- efferent neurons of the koniocellular layers of the LGN tors found a lack of spatial summation effect in blindsight are preferentially spared after V1 lesions (Cowey, 2010). using S-cone stimuli as compared with luminance stimuli Not only is the koniocellular LGN less damaged by V1 le- (Leh et al., 2006). This result, combined with others sions, neurons there may actually enhance and strengthen using colored stimuli, suggests that color may be treated their role as indicated by their change in size (Leopold, differently in blindsight than in normal vision, where V1 2012). Many of the neurons in LGN that survive retrograde input to SC is available. It is difficult to say whether these degeneration after V1 lesions are those that project directly results in hemispherectomized patients apply generally to extrastriate areas (Cowey & Stoerig, 1989). Direct pro- to blindsight because color-specific effects may depend jections from the LGN to extrastriate visual areas stem on the presence of color selective areas in extrastriate primarily from the koniocellular layers, whereas the mag- cortex (Gross et al., 2004; Gross, 1991). Nevertheless, nocellular and parvocellular layers project predominantly these results suggest that, without any cortical input to V1 (Leopold, 2012; Cowey, 2010; Hendry & Reid, available, sensitivity of SC neurons to colored stimuli is 2000). The intact subcortical input from the SC also ter- diminished. minates predominantly in the koniocellular layers of the In another effort to better isolate the S opponent LGN (Leopold, 2012; Hendry & Reid, 2000). mechanism, narrowband stimuli were used to address Intriguing evidence for the role of the SC and konio- color discrimination in blindsight (Alexander & Cowey, cellular neurons in blindsight comes from the spatial and 2010). These researchers found that color discrimination temporal response properties of these neurons. Konio- is possible, even for short wavelength stimuli. Interestingly, cellular and SC neurons, which closely resemble each other when the cone contrast of stimuli was specifically ad- (as outlined above), are similar to those most desirable dressed, discrimination appeared to be better for stimuli for eliciting blindsight, namely, low pass filtered spatial with larger effects on the S opponent system. Contrary to tuning responses with sensitivity peaks around 1 cycle/ evidence from hemispherectomized subjects, these data degree, abrupt transient stimuli, and hard edges (Alexander indicate that blindsight can make use of signals that pref- & Cowey, 2010; Weiskrantz, 2004). Thus, patterns of neu- erentially excite S-cones. ronal degeneration and visual abilities after V1 lesions Behavioral studies in monkeys provide further evi- strongly suggest an enhanced, rather than diminished, role dence for the utility of S-cone isolating information in for S-cone pathways in blindsight. blindsight. Monkeys with blindsight can make saccades to color defined targets (Yoshida et al., 2012). These tar- Neuronal Pathways for Blindsight gets include uncalibrated S-cone isolating stimuli, as de- fined in DKL color space. Although the S-cone stimulus Although the exact pathways for blindsight are not known, was not individually calibrated, Yoshida et al. (2012) per- observations of neuronal degeneration in the LGN and formed three manipulations designed to rule out stimu- retina after V1 lesions advocate a crucial role for reorgani- lus detection because of artifacts. (1) Luminance contrast zation in blindsight. Neuronal pathways for blindsight was varied to rule out the possibility of detection by lu- could be affected by the substantial reorganization that minance contrast. (2) Gaussian stimuli were used that takes place after V1 lesions (Gross et al., 2004). Evidence eliminate the effects of presenting hard edges. (3) Lumi- for the importance of reorganization stems from V1 lesions nance noise masking was used to eliminate artifacts of in infancy, which generally produce more effective blind- sudden stimulus onset, residual contrasts, and hard edge sight in monkeys (Moore, Rodman, & Gross, 2001; Moore, presentation. Despite efforts to ascribe blindsight detec- Rodman, Repp, Gross, & Mezrich, 1996). This is presum- tion of S-cone stimuli to other stimulus attributes, mon- ably because reorganization is faster and more effective keys consistently demonstrated blindsight detection of in early life. An example of differential reorganization later
Hall and Colby 1251 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00555 by guest on 28 September 2021 in life is seen in the complex task of color discrimination. depends on this pathway with S-cone stimuli. One example Color discrimination takes a considerable amount of time would be express saccades, which are thought to make to stabilize in blindsight, suggesting that reorganization of use of the direct retinotectal pathway (Yoshida et al., color systems is slow to take hold (Stoerig & Cowey, 1997). 2008, but see Schiller et al., 2008, for a counter view). Un- Although it is difficult to reconcile the contradicting results der this assumption, if express saccades can be generated of color discrimination and SC contributions to blindsight to S-cone isolating stimuli, then this would indicate that (described above), reorganization could be a confounding S-cone signals are carried in the retinotectal pathway.
factor. Reorganization of visual systems and the konio- Downloaded from http://mitprc.silverchair.com/jocn/article-pdf/26/6/1234/1781060/jocn_a_00555.pdf by MIT Libraries user on 17 May 2021 cellular system in particular is likely to have a powerful Conclusions impact on the residual visual abilities and critical structures of blindsight. Understanding how the visual system re- We found that neurons in the SC respond to individually organizes in blindsight is critical to understanding the calibrated S-cone isolating stimuli on a luminance noise- underlying mechanisms. masking background. The population of SC neurons is One of the most elusive aspects of the blindsight puzzle able to discriminate high from low S-cone contrasts and is the precise pathway(s) involved. Even after neuronal respond more strongly to appropriately chosen S-cone degeneration and reorganization, a number of visual path- than luminance stimuli. The neuronal response latency of ways remain possibilities (Leopold, 2012; Stoerig & Cowey, SC neurons correspondingly modulates with the contrast 1997). Both the LGN and pulvinar nuclei of the thalamus of an S-cone stimulus, with shorter latencies at higher project to extrastriate cortex and receive direct retinal in- contrasts. The sensitivity of SC neurons to changes in put. Both nuclei also receive input from the SC. The SC S-cone contrast depends on their level of transience, such and extrastriate visual cortex both appear to be indispen- that more transient neurons are more sensitive to changes sable for blindsight (Cowey, 2010; Yoshida et al., 2008; in contrast. Our experimental procedures provide a direct Weiskrantz, 2004; Goebel et al., 2001; Vaughan & Gross, link between our electrophysiological results and previous 1969). Recent fMRI evidence in monkeys points addition- human psychophysical studies. Our finding that S-cone ally to a critical role for the LGN. Visual stimuli induce wide- stimuli activate SC neurons rules out the possibility of spread activation of extrastriate cortex after V1 lesions blocking visual input to the SC by using S-cone isolating (Schmid et al., 2010). The critical finding is that when V1 stimuli. Therefore, further studies are required to eluci- lesions are combined with inactivation of the LGN, re- date the neuronal foundations of and SC contributions to sponses in extrastriate cortex are abolished. Our data show phenomena that have been widely studied with the use of that SC neurons are responsive to S-cone stimuli. The dis- S-cone stimuli, such as blindsight. covery that blindsight monkeys and blindsight patients in some studies are able to detect stimuli that preferentially activate S-cones would cast doubt on the well-established Acknowledgments role of the SC in blindsight if the SC were not sensitive to We would like to express our deep appreciation to Dr. Petroc S-cones. Our data show that, even during color discrimi- Sumner for his insight and guidance with the calibration and nations, the SC could retain a central role in blindsight. presentation of S-cone isolating stimuli. We thank K. McCracken and Dr. Kevin Hitchens for technical assistance and our col- Together, these findings suggest that the blindsight path- leagues at the Center for the Neural Basis of Cognition for dis- way follows a route from the SC to the koniocellular layers cussion and comments. We also thank Dr. R. Desimone for of the LGN to extrastriate cortex (Leopold, 2012) and can provision of the CORTEX program developed in his laboratory carry color signals from S-cones. This proposal completes at NIMH. This work was supported by National Institutes of a picture, whereby the SC, the extrastriate cortex, and the Health grants EY-12032 and MH-45156. Technical support was provided by Core grant EY-08908, and collection of MR images LGN are all essential to blindsight. was supported by P41RR-03631. N. Hall was also supported by a National Science Foundation IGERT award (DGE 0549352). What Pathway(s) Carries S-cone Signals to the SC? Reprint requests should be sent to Nathan Hall, Department of Neuroscience, University of Pittsburgh, 115 Mellon Institute, Our data do not address the pathway(s) that carry S-cone 4400 Fifth Avenue, Pittsburgh, PA 15213, or via e-mail: njh5@ signals to the SC. There are two major pathways that carry cnbc.cmu.edu. visual input to the SC. Either or both of these pathways could be responsible for the observed activation of SC neurons to S-cone stimuli. It has been argued that the SC REFERENCES depends on the indirect pathway via LGN to V1 to generate Alexander, I., & Cowey, A. (2010). Edges, colour and awareness saccades (Schiller, Kendall, Slocum, & Tehovnik, 2008). in blindsight. 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