We recorded responses of LGN and TRN neurons in three awake behaving macaque monkeys (Macaca mulatta). Monkeys were directed by a central cue at the point of fixation to attend to one of two peripheral visual stimuli on randomly interleaved trials (inset in ). One of these stimuli was in the receptive field (RF) of the recorded neuron. shows the responses of an example magnocellular LGN neuron (LGNm) to a light bar within the RF when attention was directed out of the RF (dashed curve, ATTout) or into the RF (solid curve, ATTin). Responses shown are from correct trials. The ATTin response falls above the ATTout response, indicating an increase in neuronal response with attention. The mean response to the same stimulus increased 12% with attention. shows the responses of a parvocellular LGN neuron (LGNp) that also increased (21%) when attention was directed into the RF.
Figure 1 Sample responses to shifts of attention in LGN and TRN. Solid traces are spike density plots of the neuron’s ATTin response (as illustrated by the “spotlight” of attention in the inset cartoon directed to the circle representing (more ...)
If a similar increase in attention were to occur in TRN, however, Crick’s hypothesized interaction between TRN and LGN encounters a problem: TRN inhibits LGN. The visual sector of TRN receives excitatory inputs from LGN, but projects modulatory inhibitory input back to LGN6–13
. Therefore, TRN responses should instead decrease with attention, reducing the inhibitory influence of the TRN on LGN, thereby causing the increase in the responses of LGN neurons that we observe. We did in fact find a decrease in the TRN visual response with attention (). When attention was directed into the RF of this TRN neuron, the mean response to the same visual stimulus was 13% less than when attention was directed out of the RF.
We have summarized the effect of attention on mean visual responses of 57 on-center LGN neurons (19 LGNm and 38 LGNp) in , and of 29 TRN neurons in . In each plot, the ordinate is the baseline ATTout response and the abscissa is the attentional modulation, ATTmod. ATTmod can be expressed either as the contrast measure (ATTin−ATTout)/(ATTin + ATTout), or the ratio of modulation (ATTin/ATTout). We have included both, with the bottom axes representing the ratio of modulation, and the top axes indicating the contrast measure of ATTmod. shows the bulk of points to the right of the vertical unity line indicating that the predominant effect of attention in LGN neurons was to increase mean responses to the visual stimulus. Distributions of ATTmod appear above the scatterplot, with small arrows indicating sample medians. In LGN, attention increased the median response 11 ± 2.6% in the magnocellular layers (p = 0.011), and 9 ± 1.1% in the parvocellular layers (p = 0.0007). All indications of variability are plus or minus one standard error of the median, and all p-values were determined using the Wilcoxon signed rank test for zero median, unless otherwise specified.
Figure 2 Effect of attention on LGN and TRN. a, Scatterplot showing mean baseline ATTout response versus attentional modulation (ATTmod) for 19 LGNm neurons (blue) and 38 LGNp neurons (red). Solid symbols are significant response changes (Wilcoxon rank-sum test, (more ...)
In contrast to LGN, values of attentional modulation in TRN () tend to lie to the left of the unity line, showing a median decrease in neuronal response with attention of 4 ± 0.6% (p = 0.004). Over our sample of neurons, the reciprocal effect of attention holds; LGN responses increase with attention whereas TRN responses decrease.
If attention modulates neuronal responses, we would not necessarily expect such modulation during trials on which the monkeys made incorrect behavioral responses. For TRN neurons with more than five error trials, responses on those trials increased by 1.5 ± 1.5% (n=18, p = 0.62). Similarly, for LGNm and LGNp neurons, respectively, responses changed by 2.3 ± 3.6% (n=11, p = 0.58) and 1.3 ± 2.6% (n=22, p = 0.71). The lack of significant response modulation on incorrect trials provides further evidence that the factor enabling the monkeys to perform the task correctly was the same one modulating neuronal responses: visual attention.
We found no significant modulation of the background activity preceding the initial visual response or in the latency or duration of the initial visual response in either LGN or TRN. To observe any residual effect of attention beyond the initial visual response, we examined mean neuronal responses from 100 ms before stimuli appeared to 500 ms after they appeared (the shortest presentation time common to all trials). For each neuron, we normalized the response to the neuron’s maximum firing rate. shows the mean normalized response for each area with solid curves for the ATTin condition and dashed curves for the ATTout condition. We calculated ATTmod for the six 100 ms time epochs in this time scale. shows ATTmod (as ATTin/ATTout) over time. Median changes for each area are connected across epochs with solid lines, and error bars denote ± 1 standard error of the median. Significant changes within an epoch are denoted by colored asterisks.
Figure 3 Time courses of visual and attentional influences. a, Mean normalized ATTin (solid curves) and ATTout (dashed curves) responses for each area. Each curve is the mean normalized spike density plot over all neurons in an area. Mean responses have been smoothed (more ...)
All areas demonstrate a significant response modulation in the initial 100 ms epoch after the stimuli appear. However, this modulation disappears in the next 100 ms epoch, but LGNm and LGNp show a second, later period of modulation that becomes significant in both divisions as time progresses. Also, both LGNm and LGNp showed significant attentional modulation just before the monkey needed to make a decision about the stimulus. Note that in contrast to LGN, TRN had no second period of attentional modulation.
Because only the initial visual response in TRN is modulated by attention, measuring over the whole 500 ms period would have yielded a much smaller modulation in TRN (−1.8%) that would not have been significant (p = 0.31). However, due to the second phase of modulation in LGN, we still would have measured attentional modulation of 13% in LGNm (p = 0.014) and 8.1% in LGNp (p < 0.0001), but the influence of TRN on the initial visual response would have gone undetected.
We see that careful consideration of responses over time is critical to detect the attentional effects in TRN, but analysis of the interactions between LGN and TRN requires an even more precise examination of response timing. To compare visual response latencies, shows the mean normalized initial responses for neurons in each area aligned on stimulus onset. To determine the significance of visual latency differences, we performed a bootstrap analysis (see Supplementary Notes
) yielding estimates of the median visual latency in each area, and the significance of differences between areas using the Wilcoxon rank-sum test for equal medians. Although TRN responses (median latency 22 ± 0.92 ms) begin well before those in LGNp (p < 0.001, median latency 37 ± 1.43 ms), LGNm neurons (median latency 21 ± 1.25 ms) tend to respond before TRN neurons (p < 0.001).
Figure 4 Latencies of visual and attentional influences. a, First 100 ms of the visual responses from . Thick lines are sample descriptive fits to ATTin responses from the bootstrap analysis. Arrows indicate median visual latencies. b, Latency of attentional (more ...)
To track the timing of attentional modulation in each area, we represented the effect of attention in as the difference between the mean ATTin and ATTout curves from . The latency of attentional modulation was obtained from a similar bootstrap analysis. Whereas the visual response appears first in LGNm, shows that attentional modulation occurs first in TRN (22 ± 0.37 ms), 4 ms before LGNm (26 ± 0.31 ms, p < 0.001). The attentional effect shows up significantly later in LGNp (37 ± 0.31 ms) than either TRN or LGNm (p < 0.001 for both). Therefore, even though LGNm visual responses precede those of TRN (consistent with LGNm driving the visual response in TRN), attention affects TRN responses first, consistent with attentional modulation in LGN coming from TRN.
In conclusion, we find that attention modulates thalamic visual responses in two phases: an initial modulation that enhances LGN responses and attenuates TRN responses, followed by a slowly building later enhancement limited to LGN. Until now, demonstration of attentional modulation of LGN neurons has been limited to preliminary experiments on monkey14
and fMRI studies in humans15
. For the TRN, in addition to the recent growth in anatomical and cellular studies of monkey visual TRN6, 8, 9, 13
, we recently found attentional modulation of neuronal activity in visual TRN during a visual/auditory attention task16
. The differences between the visual/auditory attention task and the current task, along with a comparison of their results, are found in the Supplementary Discussion
The initial LGN modulation might provide a substantial fraction of the modulation seen subsequently in cortical area V117–23
. While it is difficult to compare across studies, the approximately 10% increase in responses we find in LGN is similar to the 6.9% median increase across V1 neurons17
, and the 8.9% median increase in V1 simple cells18
. The presence of the initial modulation in both TRN and LGN, their reciprocal increase and decrease, and the timing of their visual and attentional responses are consistent with TRN serving as the source of the initial LGN modulation as proposed by Crick.
The later attentional effects in LGN, and effects others have reported in higher cortical visual areas, might be more closely related to goal-directed attention which frequently also develops later in the visual response particularly in higher cortical areas2, 4, 24
. This later modulation in LGN might in fact reflect feedback from cortex onto the LGN25, 26
via the established connections from V1 layer 625, 27
, whereas the initial modulation in LGN by way of TRN may have its origins in subcortical structures, possibly including the superior colliculus28–30
. While obviously separate in time course, the two phases of modulation may represent two distinct attentional influences, and may be early indicators for identifying and distinguishing feed-forward and feedback visual attentional mechanisms.