Causal links between dorsal medial superior temporal area neurons and multisensory heading perception

Abstract

The dorsal medial superior temporal area (MSTd) in the extrastriate visual cortex is thought to play an important role in heading perception because neurons in this area are tuned to both optic flow and vestibular signals. MSTd neurons also show significant correlations with perceptual judgments during a fine heading direction discrimination task. To test for a causal link with heading perception, we used microstimulation and reversible inactivation techniques to artificially perturb MSTd activity while monitoring behavioral performance. Electrical microstimulation significantly biased monkeys' heading percepts based on optic flow, but did not significantly impact vestibular heading judgments. The latter result may be due to the fact that vestibular heading preferences in MSTd are more weakly clustered than visual preferences and multiunit tuning for vestibular stimuli is weak. Reversible chemical inactivation, however, increased behavioral thresholds when heading judgments were based on either optic flow or vestibular cues, although the magnitude of the effects was substantially stronger for optic flow. Behavioral deficits in a combined visual/vestibular stimulus condition were intermediate between the single-cue effects. Despite deficits in discrimination thresholds, animals were able to combine visual and vestibular cues near optimally, even after large bilateral muscimol injections into MSTd. Simulations show that the overall pattern of results following inactivation is consistent with a mixture of contributions from MSTd and other areas with vestibular-dominant tuning for heading. Our results support a causal link between MSTd neurons and multisensory heading perception but suggest that other multisensory brain areas also contribute.

Figure 1.

Heading discrimination task and hypothesized changes in behavioral performance. A, Monkeys seated on a motion platform were translated forward, and heading angle, α, was varied around straight ahead. A projector mounted on the platform displayed images of a 3D star field and provided optic flow cues. B, Timing of events in the electrical microstimulation experiment. After fixating a visual target, the monkey experienced forward motion with a small leftward or rightward component, and subsequently reported his perceived heading (“left” vs “right”) by making a saccadic eye movement to one of two targets. Microstimulation was applied on one-half of the trials, randomly interleaved with control trials. The amplitude of the microstimulation pulse train followed a Gaussian profile with a peak of 20 μA, similar to the Gaussian velocity profile of the heading stimulus. C, Predicted effects of microstimulation on heading discrimination performance. If MU activity at the stimulation site has a leftward heading preference, microstimulation should lead to more leftward choices such that the psychometric function is shifted to the right. In contrast, stimulating sites with a rightward heading preference should cause a leftward shift of the psychometric function. D, Predicted effects of reversible inactivation on heading discrimination performance. Muscimol injection suppresses neural activity (inset) in a large region and is expected to deteriorate the precision of heading discrimination, leading to a shallower psychometric function.

Figure 2.

Examples of two microstimulation experiments. A, B, Heading tuning of MU activity at each stimulation site in response to vestibular (black), visual (low coherence, red; high coherence, magenta) and combined (green) stimuli. Error bars indicate SEM. Gray highlight, Heading range tested in the discrimination task. C, D, Psychometric functions for stimulated (dashed curves) and nonstimulated (solid curves) trials in response to vestibular (black), low-coherence visual (red), and combined (green) stimuli.

Figure 3.

Clustering of visual (A) and vestibular (B) MU activity in area MSTd. Distributions of correlation coefficients of MU tuning across sites at different distances along an electrode penetration. The filled bars illustrate correlation coefficients significantly different from zero. The arrows illustrate median correlation values, and the asterisks mark cases for which the mean correlation coefficient is significantly different from zero (p < 0.05, sign test). The dashed vertical lines denote zero correlation.

Figure 4.

Summary of microstimulation-induced shifts in the PSE of animals C and S. Data are shown separately for visual (A, B), vestibular (C, D), and combined (E, F) conditions. Positive PSE values represent shifts in the direction predicted by the heading tuning of MU activity. Negative PSE values represent shifts in the opposite direction. The filled and open bars represented significant and nonsignificant PSE shifts, respectively. Arrows, Mean PSE shift. The dashed vertical lines mark zero PSE shift.

Figure 5.

Relationship between the size of microstimulation effect (induced PSE shift) and MU discriminability for heading. For each stimulation site, a d′ value that characterizes heading selectivity around straight forward was computed from the responses at −22.5 and +22.5°. The filled and unfilled symbols denote significant and nonsignificant PSE shifts, respectively (monkey C, circles; monkey S, triangles). Data are shown separately for visual (red), vestibular (black), and combined (green) conditions. The top and right panels show marginal distributions of |d′| and |ΔPSE| (on log scales). The arrows mark the respective geometric means.

Figure 6.

Effects of microstimulation on heading discrimination thresholds. A, B, Psychophysical thresholds during control (gray) and microstimulation (black) trials for animals C and S. Error bars indicate SEM. C, Relationship between the change in PSE and threshold on a session by session basis (data from the visual stimulus condition). Animal S (filled circles) had significantly larger PSE shifts (median, 1.608°) than animal C (open squares; median, 0.649°; p ≪ 0.001, Mann–Whitney U test), and this may explain the significant visual threshold changes in monkey S (B, asterisk). D, Comparison of actual combined thresholds and those predicted from optimal cue integration (Eq. 2). Black symbols, Microstimulation condition; gray symbols, control condition. Squares, monkey C; circles, monkey S.

Figure 7.

An example inactivation experiment. Psychometric functions were collected during four separate sessions: a control block before the day of muscimol injection (Pre, dashed curves and cross symbols), a block immediately after inactivation (0 h, orange), a block 12 h after inactivation (12 h, red), and a recovery block 36 h after inactivation (36 h, black solid curves and open symbols). Psychometric functions are shown for each of visual (A), vestibular (B), and combined (C) conditions. These data were collected following four bilateral injections of muscimol (2 in each hemisphere), each having a volume of 2 μl and a concentration of 10 μg/μl (see Materials and Methods).

Figure 8.

Summary of inactivation-induced increases in psychophysical thresholds of animals S (circles), J (triangles), and C (squares); data were collected following four bilateral muscimol injections (see Materials and Methods). Data are shown separately for visual (A, D), vestibular (B, E), and combined (C, F) conditions. The abscissa in each panel marks the four different time points at which data were collected: Pre, 0, 12, or 36 h. Top panels (A–C) show data from individual experiments, whereas bottom panels (D–F, open bars) show average normalized thresholds (normalized by dividing the threshold at each time point by that from the Pre block). The asterisks mark normalized thresholds significantly greater than unity (*p < 0.05; **p < 0.01; ***p < 0.001). Error bars indicate SEM. For comparison, mean normalized thresholds from saline control injections are superimposed (D–F, gray bars).

Figure 9.

Summary of changes in psychophysical thresholds following various configurations of muscimol injections: A–C, single site; D–F, two injections in the same hemisphere; G–I, two injections, one per hemisphere. Each injection contained 2 μl of muscimol at a concentration of 10 μg/μl. Note that these alternative injection configurations were performed only in animals C and S before the four-site bilateral injections shown in Figure 7, and 12 h data were not collected in these experiments. The format is as in Figure 8.

Figure 10.

Cue integration effects before and after inactivation (4 injections, bilateral). Data for low coherence (A, B) and high coherence (C, D) from monkeys J and C. Data are shown as mean (±SEM) threshold for the three stimulus conditions, along with the prediction from optimal cue integration (Eq. 2). The gray bars represent control thresholds (from Pre and 36 h sessions pooled together). The black bars represent inactivation thresholds (from 0 and 12 h blocks pooled together). E, F, Comparison between actual and predicted combined thresholds for the control and inactivation sessions, respectively. Blue symbols, Low coherence; red symbols, high coherence. Triangles, Monkey J; squares, monkey C.

Figure 11.

Cue reweighting effects before and after inactivation (4 injections, bilateral). A, Stimulus arrangement during cue-conflict trials. Positive Δ (left) indicates that the visual heading is deviated to the right of the vestibular heading, and vice versa for negative Δ (middle). For a given Δ (right), heading angle was defined as the midpoint between the visual and vestibular headings, which were varied together in fine steps around straight forward. B–D, Example psychometric functions from one experimental session in the single-cue conditions (B), combined condition at low motion coherence (C), and combined condition at high motion coherence (D). E, The actual vestibular weight (w_{vest_actual}) (see Materials and Methods) as a function of time relative to drug injection for four inactivation experiments performed with monkey S. Each experiment contains interleaved low (20%; blue) and high (70%; red) motion coherences. F, G, Comparison between actual and predicted vestibular weights (see Materials and Methods) estimated from control and inactivation sessions, respectively. Blue symbols, Low coherence; red symbols, high coherence.

Figure 12.

A simple simulation of the effects of inactivation on behavior. Two populations of 1000 hypothetical neurons with cosine heading tuning and uniformly distributed heading preferences were simulated: one population representing area MSTd and the other population representing an area (such as VPS) with vestibular-dominant heading tuning. A, Amplitudes of model tuning curves were chosen such that the MSTd-like neurons had heading tuning that was visual dominant (amplitudes were drawn from Poisson distributions with a mean of 20 for visual tuning and a mean of 10 for vestibular tuning). Tuning curves for the VPS-like neurons had mean amplitudes of 10 for visual tuning and 20 for vestibular tuning. A decoder (based on computing population Fisher information) (Gu et al., 2010) pools heading information either from only area MSTd (left column) or from both areas (right column). B, Predicted psychophysical thresholds as a function of the proportion of neurons that were inactivated (excluded from decoding) in model area MSTd. C, Same format as in B, but instead shows the ratios of predicted thresholds across various stimulus conditions.