Nonlinear Spectrotemporal Interactions Underlying Selectivity for Complex Sounds in Auditory Cortex

Example A1 neuron that displayed selectivity to repetitive stimuli. A, Subunits were observed at 8.5 kHz (BF) spaced at ∼50 ms intervals. Another significant subunit was located 0.25 octaves below BF occurring ∼25 ms earlier. B, Spike rasters of this neuron's response to Gaussian pulse trains (left) and lFM sweep trains (right) (5 sweeps per train). Responses were sustained throughout stimulus duration. C, Consistent with the nonlinear response map, this unit was tuned to interclick intervals of 40 and 80 ms when tested with Gaussian pulse train stimuli at BF (carrier frequency 8.5 kHz, click width SD 4 ms; mean ± 1 SD plotted). ICI, Interclick interval. D, The unit preferred 50-ms-long upward lFM sweeps trains ∼8.5 kHz with a preferred intersweep interval of 50 ms, also consistent with A. At least two sweeps were required to elicit a response. Darkest line corresponds to 7 sweeps in train, lightest line to a single sweep. ISI, Intersweep interval. Colormap, contours and raster conventions as in Figure 1. “u” and “d” refer to upward and downward lFM sweeps and are alternated along the axis.

Example A1 neuron showing purely spectral combination sensitivity. A, Nonlinear interaction map for this neuron showed excitatory subunits located 1/8 oct. above and below BF at coincident onset times with the BF pip. B, Spike rasters of this neuron's response to BPN of different BWs (left) and sAM at different modulation rates (AM rate; right). C, This unit was tuned to a bandwidth of ∼0.4 oct. centered at BF and BL, consistent with the nonlinear map obtained. D, Interestingly, this unit was narrowly tuned to sAM tones at 5.2 kHz modulated at 512 Hz. It should be noted that at a BF of 5.2 kHz, this amplitude modulation at 512 Hz produces spectral sidebands that are ∼1/8 oct. away from BF. Thus, these responses are also consistent with the nonlinear map in A. Error bars correspond to ± 1 SEM; dashed orange line is spontaneous rate. Colormap, Contours and raster conventions as in Figure 1.

Nonlinear spectrotemporal interactions underlie complex feature selectivity in A1. A, Nonlinear interaction map of another example A1 neuron that showed strong nonlinear interactions around a BF of 6.5 kHz. B, However, this unit did not respond to a wide variety of commonly used stimuli. Red circles are responses to two-pip stimuli and pink circles are responses to pure tones. Each dot is driven response rate (after subtracting spontaneous rate) to an individual stimulus belonging to that particular stimulus set. Abbreviations used in addition to those defined in text are as follows: FRA, frequency response area (tones); Col., colony noise (environmental sounds from monkey colony); Voc., marmoset vocalizations, BW − BPN of varying bandwidths. C, Raster of two-pip responses corresponding to map in A showing robust spiking occurred after integration of both pips. Colormap, Contours and raster conventions as in Figure 1.

Response enhancement by two-pip stimuli in nonlinear A1 neurons. A, Nonlinear neurons were not responsive to tones (median = 0 spikes/s, gray histogram). However, using two-pip stimuli, we could drive these neurons to a median of 24 spikes/s (black histogram), comparable to the median pure tone response (at BF) of tone-responsive neurons in the awake marmoset. (**p < 0.01; Wilcoxon rank-sum test). B, When we quantified degree of nonlinearity (see Materials and Methods), we observed a median 250% facilitation over the sum of linear components. C, Histograms of precision in frequency and time of the second-order subunits (half-maximal extent). Median spectral and temporal precision were 0.125 oct. and 12.5 ms respectively.

Location and properties of nonlinear neurons in A1. A, Distribution of absolute depth (from dural surface) and relative depth (from first neuron encountered) of nonlinear (black dots) and tone-responsive (gray dots) units. Nonlinear units were located at shallower cortical depths compared with tone-responsive units (histograms of absolute and relative depths are on margins, numbers are medians; *p < 0.05, **p < 0.01, Wilcoxon rank-sum test). This suggested that nonlinear neurons may be localized to superficial cortical layers. B, Distribution of all observed subunits plotted relative to normalized BF. Gray ellipses are locations of statistically significant nonlinear subunits; shading corresponds to the percentage of facilitation. Most subunits were located <0.5 octaves away from BF suggesting a local computation. Most subunits also occurred within 50 ms of the BF pip.

Generality and robustness of A1 nonlinear neurons. A, We did not find any differences in the distributions of BFs (top) or BLs (bottom) between nonlinear neurons (black histograms) and tone-responsive neurons (gray histograms) suggesting that the observed phenomenon was a general computation (n.s., not significant). B, High nonlinearity observed was not a consequence of using short stimuli to obtain linear response rates. When responses to 100-ms-long pure tones were used to compute single-tone response rates, we still observed significant nonlinear facilitation when compared with two-pip responses computed using 20–40 ms pips. The neuron falling below the diagonal (y = x line) presumably exhibited a stimulus length effect. C, Predicted versus actual preferred lFM velocities of a subset of nonlinear units (n = 22; **p < 0.01). Inset, Predicted versus actual preferred BWs of BPN stimuli in another subset of nonlinear units (n = 8; not significant). D, Distribution of actual p values from all neurons that met our initial screening criterion of peak p < 0.05, modified permutation test (n = 41, gray histogram). Dotted line indicates the Bonferroni-corrected p value criterion for the most common stimulus set (n = 289 stimuli). Thirty-nine of 41 neurons met this criterion.